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Aim: Routine alcohol testing of practicing physicians remains controversial since there are no uniform guidelines or legal regulations in the medical field. Our aim was to quantitatively study the acute and next-morning effects of breath alcohol concentration (BAC)-adjusted alcohol intake on overall simulated surgical performance and microtremor among senior vitreoretinal surgeons., Methods: This prospective cohort study included 11 vitreoretinal surgeons (>10 years practice). Surgical performance was first assessed using the Eyesi surgical simulator following same-day alcohol consumption producing a BAC reading of 0.06%-0.10% (low-dose), followed by 0.11%-0.15% (high-dose). Dexterity was then evaluated after a 'night out' producing a high-dose BAC combined with a night's sleep. Changes in the total score (0-700, worst-best) and tremor (0-100, best-worst) were measured., Results: Surgeon performance declined after high-dose alcohol compared with low-dose alcohol (-8.60±10.77 vs -1.21±7.71, p=0.04, respectively). The performance during hangover was similar to low-dose alcohol (-1.76±14.47 vs -1.21±7.71, p=1.00, respectively). The performance during hangover tended to be better than after high-dose alcohol (-1.76±14.47 vs -8.60±10.77, p=0.09, respectively). Tremor increased during hangover compared with low-dose alcohol (7.33±21.65 vs -10.31±10.73, p=0.03, respectively). A trend toward greater tremor during hangover occurred compared with high-dose alcohol (7.33±21.65 vs -4.12±17.17, p=0.08, respectively)., Conclusion: Alcohol-related decline in simulated surgical dexterity among senior vitreoretinal surgeons was dose-dependent. Dexterity improved the following morning but remained comparable to after low-dose alcohol ingestion. Tremor increased during hangover compared with same-day intoxication. Further studies are needed to investigate extrapolations of these data to a real surgical environment regarding patient safety and surgeon performance., Competing Interests: Competing interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate novice and senior vitreoretinal surgeons after various exposures. Multiple comparisons ranked the importance of these exposures for surgical dexterity based on experience., Methods: This prospective cohort study included 15 novice and 11 senior vitreoretinal surgeons (<2 and >10 years' practice, respectively). Eyesi-simulator tasks were performed after each exposure. Day 1, placebo, 2.5 mg/kg caffeine, and 5.0 mg/kg caffeine; day 2, placebo, 0.2 mg/kg propranolol, and 0.6 mg/kg propranolol; day 3, baseline simulation, breathalyzer readings of 0.06% to 0.10% and 0.11% to 0.15% blood alcohol concentrations; day 4, baseline simulation, push-up sets with 50% and 85% repetitions maximum; and day 5, 3-hour sleep deprivation. Eyesi-generated score (0-700, worst-best), out-of-tolerance tremor (0-100, best-worst), task completion time (minutes), and intraocular pathway (in millimeters) were measured., Results: Novice surgeons performed worse after caffeine (-29.53, 95% confidence interval [CI]: -57.80 to -1.27, P = 0.041) and alcohol (-51.33, 95% CI: -80.49 to -22.16, P = 0.001) consumption. Alcohol caused longer intraocular instrument movement pathways (212.84 mm, 95% CI: 34.03-391.65 mm, P = 0.02) and greater tremor (7.72, 95% CI: 0.74-14.70, P = 0.003) among novices. Sleep deprivation negatively affected novice performance time (2.57 minutes, 95% CI: 1.09-4.05 minutes, P = 0.001) and tremor (8.62, 95% CI: 0.80-16.45, P = 0.03); however, their speed increased after propranolol (-1.43 minutes, 95% CI: -2.71 to -0.15 minutes, P = 0.029). Senior surgeons' scores deteriorated only following alcohol consumption (-47.36, 95% CI: -80.37 to -14.36, P = 0.005)., Conclusion: Alcohol compromised all participants despite their expertise level. Experience negated the effects of caffeine, propranolol, exercise, and sleep deprivation on surgical skills.

Purpose: To assess the impact of a 3-hour polysomnography (PSG)-recorded night of sleep deprivation on next-morning simulated microsurgical skills among vitreoretinal (VR) surgeons with different levels of surgical experience and associate the sleep parameters obtained by PSG with Eyesi-generated performance., Design: Self-controlled cohort study., Participants: Eleven junior VR surgery fellows with < 2 years of surgical experience and 11 senior surgeons with > 10 years of surgical practice., Methods: Surgical performance was assessed at 7am after a 3-hour sleep-deprived night using the Eyesi simulator and compared with each subject's baseline performance., Main Outcome Measures: Changes in Eyesi-generated score (0-700, worst to best), time for task completion (minutes), tremor-specific score (0-100, worst to best), and out-of-tolerance tremor percentage. Polysomnography was recorded during sleep deprivation., Results: Novice surgeons had worse simulated surgical performance after sleep deprivation compared with self-controlled baseline dexterity in the total score (559.1 ± 39.3 vs. 593.8 ± 31.7; P = 0.041), time for task completion (13.59 ± 3.87 minutes vs. 10.96 ± 1.95 minutes; P = 0.027), tremor-specific score (53.8 ± 19.7 vs. 70.0 ± 15.3; P = 0.031), and out-of-tolerance tremor (37.7% ± 11.9% vs. 28.0% ± 9.2%; P = 0.031), whereas no performance differences were detected in those parameters among the senior surgeons before and after sleep deprivation (P ≥ 0.05). Time for task completion increased by 26% (P = 0.048) in the post-sleep deprivation simulation sessions for all participants with a high apnea-hypopnea index (AHI) and by 37% (P = 0.008) among surgeons with fragmented sleep compared with those with normal AHI and < 10 arousals per hour, respectively. Fragmented sleep was the only polysomnographic parameter associated with a worse Eyesi-generated score, with a 10% (P = 0.005) decrease the following morning., Conclusions: This study detected impaired simulated surgical dexterity among novice surgeons after acute sleep deprivation, whereas senior surgeons maintained their surgical performance, suggesting that the impact of poor sleep quality on surgical skills is offset by increased experience. When considering the 2 study groups together, sleep fragmentation and AHI were associated with jeopardized surgical performance after sleep deprivation., Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background/objectives: Tremor and expertise are potentially influenced variables in vitreoretinal surgery. We investigated whether surgeon experience impacts the association of microsurgical performance with caffeine and β-blockers weight-adjusted intake., Subjects/methods: Novice and senior surgeons (<2 and >10 practice years, respectively) were recruited in this self-controlled, cross-sectional study. A simulator's task sequence was repeated over 2 days, 30 min after the following exposures: day 1, placebo, 2.5 mg/kg caffeine, 5.0 mg/kg caffeine, and 0.6 mg/kg propranolol; and day 2, placebo, 0.2 mg/kg propranolol, 0.6 mg/kg propranolol, and 5.0 mg/kg caffeine. Outcomes were total score (0-700, worst-best), simulation time (minutes), intraocular trajectory (centimeters), and tremor-specific score (0-100, worst-best)., Results: We recruited 15 novices (9 men [60%], 1.33 ± 0.49 practice years) and 11 seniors (8 men [72.7%], 16.00 ± 4.24 practice years). Novices performed worse after 2.5 mg/kg caffeine and improved following 0.2 mg/kg propranolol in total score (557 vs. 617, p = 0.009), trajectory (229.86 vs. 208.07, p = 0.048), time (14.9 vs. 12.7, p = 0.048), and tremor-score (55 vs. 75, p = 0.009). Surgical performance improved with propranolol post-caffeine but remained worse than 0.2 mg/kg propranolol in total score (570 vs. 617, p = 0.014), trajectory (226.59 vs. 208.07, p = 0.033), and tremor-score (50 vs. 75, p = 0.029). Seniors' tremor-score was lower after 2.5 mg/kg caffeine compared to 0.2 mg/kg propranolol (8 vs. 37, p = 0.015). Tremor-score following propranolol post-caffeine remained inferior to 0.6 mg/kg propranolol alone (17 vs. 38, p = 0.012)., Conclusion: While caffeine and propranolol were associated with performance changes among novices, only tremor was affected in seniors, without dexterity changes. The pharmacologic exposure impact on surgical dexterity seems to be offset by increased experience., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background/aims: Fetal haemoglobin (HbF) has an oxyhaemoglobin dissociation curve that may affect systemic oxygenation and the development of retinopathy of prematurity (ROP). The study aim is to characterise the effects of HbF levels on systemic oxygenation and ROP development., Methods: Prospective study conducted from 1 September 2017 through 31 December 2018 at the Johns Hopkins NICU. Preterm infants with HbF measured at birth, 31, 34 and 37 weeks post-menstrual age (PMA), complete blood gas and SpO 2 recorded up to 42 weeks PMA, and at least one ROP exam were included., Results: Sixty-four preterm infants were enrolled. Higher HbF was associated with significantly higher SpO 2 , lower PCO 2 , lower FiO 2 from birth to 31 weeks PMA and 31 to 34 weeks PMA (r s =0.51, r s =-0.62 and r s =-0.63; p<0.0001 and r s =0.71, r s =-0.58 and r s =-0.79; p<0.0001, respectively). To maintain oxygen saturation goals set by the neonatal intensive care unit, higher median FiO 2 was required for HbF in the lowest tercile from birth compared with HbF in the highest tercile to 31 weeks and 31 to 34 weeks PMA; FiO 2 =35 (21-100) versus 21 (21-30) p<0.006 and FiO 2 =30 (28-100) versus 21 (21-30) p<0.001, respectively. Preterm infants with ROP had poorer indices of systemic oxygenation, as measured by median levels of SpO2 and PCO 2 , and lower levels of HbF (p<0.039 and p<0.0001, respectively) up to 34 weeks PMA., Conclusion: Low HbF levels correlated with poor oxygenation indices and increased risk for ROP. O 2 saturation goals to prevent ROP may need to incorporate relative amount of HbF., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To describe the vitreoretinal interface in vitreomacular traction (VMT) by using novel optical coherence tomography (OCT) methods; wide-angle montage, and pseudomotion OCT imaging systems., Design: Observational case series., Methods: Wide-angle montage OCT images of horizontal and vertical scans through the fovea were acquired in 50 eyes of 46 consecutive patients with VMT. Baseline fundus scans were obtained. These were followed by scans acquired with an eye-tracking system performed immediately after vertical and horizontal eye movements. Three scans were then superimposed to compare changes in the contour and position of the posterior vitreous., Results: The subjects were classified as VMT with ("proliferative"; 48.0%) and without ("nonproliferative"; 52.0%) thickened posterior vitreous. Epiretinal membrane was observed in 26.9% of nonproliferative and 95.8% of proliferative VMT eyes (P = 3.6 × 10 -7 ). No eye of proliferative and 57.7% of nonproliferative VMT eyes had wavy contoured posterior vitreous (P = 4.0 × 10 -6 ). None with proliferative VMT, but 91.7% of nonproliferative VMT eyes, showed motion induced changes of posterior vitreous following eye movement (P = 2.0 × 10 -8 ). The posterior vitreous detachment extended beyond the scanned area in 34.6% of nonproliferative and 8.3% of proliferative VMT eyes (P = .040)., Conclusions: By dynamically evaluating the vitreoretinal interface of patients with VMT, the static contraction forces of a thickened posterior vitreous at the macula are implicated in proliferative VMT. This contractile force is not strongly implicated in the majority of VMT eyes with nontaut and more mobile vitreous (nonproliferative VMT). VMT and its associated complications are determined by at least 2 different pathophysiological mechanisms., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The development and integration of intraoperative optical coherence tomography (iOCT) into modern operating rooms has motivated novel procedures directed at improving the outcome of ophthalmic surgeries. Although computer-assisted algorithms could further advance such interventions, the limited availability and accessibility of iOCT systems constrains the generation of dedicated data sets. This paper introduces a novel framework combining a virtual setup and deep learning algorithms to generate synthetic iOCT data in a simulated environment. The virtual setup reproduces the geometry of retinal layers extracted from real data and allows the integration of virtual microsurgical instrument models. Our scene rendering approach extracts information from the environment and considers iOCT typical imaging artifacts to generate cross-sectional label maps, which in turn are used to synthesize iOCT B-scans via a generative adversarial network. In our experiments we investigate the similarity between real and synthetic images, show the relevance of using the generated data for image-guided interventions and demonstrate the potential of 3D iOCT data synthesis., Competing Interests: The authors declare that there are no conflicts of interest related to this article., (© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Retinal ischemia characterizes the underlying pathology in a multitude of retinal diseases that can ultimately lead to vision loss. A variety of novel imaging modalities have been developed to characterize retinal ischemia by measuring retinal oxygenation and blood flow in-vivo. These technologies offer valuable insight into the earliest pathophysiologic changes within the retina and provide physicians and researchers with new diagnostic and monitoring capabilities. Future retinal imaging technologies with the capability to provide affordable, noninvasive, and comprehensive data on oxygen saturation, vasculature, and blood flow mechanics are needed. This review will highlight current and future trends in multimodal imaging to assess retinal blood flow and oxygenation., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: To describe the initiation of posterior vitreous detachment (PVD) in the eyes of normal individuals, under 20 years of age, using wide-angle optical coherence tomography (OCT)., Methods: This is an observational cross-sectional study. Montaged images of horizontal and vertical OCT scans were obtained in 63 healthy eyes of 35 consecutive subjects ranging in age from 4 to 17 years., Results: Forty-five eyes (71.4%) had obvious PVD, defined as a contiguous line of posterior cortical vitreous separated from the surface of the retina. Eighteen eyes (28.6%) had no PVD. The mean age of the individuals without PVD was significantly younger than those with PVD (P = 0.008). The spatial distribution of PVD initiation was highest in the superior quadrants, with the nasal, inferior, septum papillomaculae, and temporal quadrants following in descending order of frequency (P < 0.001). PVD was observed to begin anterior to the premacular liquefied lacuna, where the vitreous gel directly adheres to the vitreoretinal interface. In the majority of subjects (80.6%), PVD was initiated anterior to the vascular arcades., Conclusions: PVD can be observed by OCT to begin in the first and second decade of life. It begins in the mid-peripheral vitreous, most frequently in the superior quadrants anterior to the vascular arcades. In this study, all PVDs originated outside of the macular liquefied lacunae, where the vitreous gel adheres directly to the retina.

Purpose: To quantitatively analyze and compare the novice vitreoretinal surgeons' performance after various types of external exposures., Methods: This prospective, self-controlled, cross-sectional study included 15 vitreoretinal fellows with less than 2 years of experience. Surgical performance was assessed using the Eyesi simulator after each exposure: Day 1, placebo, 2.5, and 5 mg/kg caffeine; Day 2, placebo, 0.2, and 0.6 mg/kg propranolol; Day 3, baseline simulation, breathalyzer reading of 0.06% to 0.10% and 0.11% to 0.15% blood alcohol concentration; Day 4, baseline simulation, push-up sets with 50% and 85% repetition maximum; Day 5, 3-hour sleep deprivation. Eyesi-generated total scores were the main outcome measured (0-700, worst to best)., Results: Performances worsened after increasing alcohol exposure based on the total score (χ2 = 7; degrees of freedom = 2; P = 0.03). Blood alcohol concentration 0.06% to 0.10% and 0.11% to 0.15% was associated with diminished performance compared with improvements after propranolol 0.6 and 0.2 mg/kg, respectively (∆1 = -22 vs. ∆2 = +13; P = 0.02; ∆1 = -43 vs. ∆2 = +23; P = 0.01). Propranolol 0.6 mg/kg was positively associated with the total score, compared with deterioration after 2.5 mg/kg caffeine (∆1 = +7 vs. ∆2 = -13; P = 0.03)., Conclusion: Surgical performance diminished dose dependently after alcohol. Caffeine 2.5 mg/kg was negatively associated with dexterity, and performance improved after 0.2 mg/kg propranolol. No changes occurred after short-term exercise or acute 3-hour sleep deprivation.

We conducted a case-control study using the Eyesi simulator to assess the surgical performance of 24 chronic cocaine users (CCUs) and 24 sex-/age-matched controls to numerically quantify ophthalmic microsurgical simulator performance and fine motor deficiencies. The inclusion criteria were no exposure to illicit drugs other than cocaine, marijuana, or alcohol within the previous month and no health conditions that could impact manual task performance. The outcomes included surgical scores (0-100, worst-best) and task completion time (minutes). Fisher's exact test, analysis of variance, Mann-Whitney U test, and Kruskal-Wallis test followed by Dunn-Bonferroni post-hoc were conducted for statistical analysis. The Eyesi scores were lower among CCUs compared to controls for bimanual tasks (4.50 ± 14.30 vs. 18.46 ± 26.64, p = 0.012), for exercises demanding upper and lower limb coordination (both hands and two foot pedals, respectively) (74.13 ± 35.01 vs. 85.21 ± 24.1, p = 0.045), and in the overall score for all three tasks (27.38 ± 15.06 vs. 39.5 ± 18.66, p = 0.021). CCUs took longer to complete tasks when performing exercises demanding upper and lower limb coordination compared to controls (1.26 ± 0.38 vs. 1.02 ± 0.44 min, p = 0.006). Individuals who used cocaine during the previous month had an independent lower bimanual score compared to controls (1.42 ± 4.91 vs. 18.46 ± 26.64, p = 0.018). No differences in performance among the CCUs were attributable to sporadic cannabis or alcohol use. Chronic use of cocaine negatively impacted fine dexterity as measured by bimanual tasks or maneuvers that required simultaneous coordination of the upper and lower limbs. This was most notable among individuals who used cocaine during the 1-month period before the simulation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Importance: Little evidence exists for prediction error in iris-sutured intraocular lenses., Background: To determine the magnitude of prediction error in iris-sutured intraocular lenses, associated factors and their long-term stability., Design: Retrospective, nonrandomized, noncomparative case series conducted at the Wilmer Eye Institute (Baltimore, Maryland, United States)., Participants: Adult patients with subluxated intraocular lenses that underwent iris-suture fixation between January 2000 and December 2014 by a single surgeon. Pregnant women, children (below the age of 18) and cases with follow-up under 1 month were excluded., Methods: Prediction error was calculated in 60 eyes and survival analysis was performed on 99 eyes., Main Outcome Measures: Prediction error (the difference between the postoperative manifest refraction in spherical equivalent and the spherical equivalent predicted by the Barrett Universal II, Holladay 2 and SRK/T formulas), preoperative and postoperative distance-corrected visual acuity, manifest refraction, frequency of postoperative complications and time until re-subluxation., Results: Mean prediction error using the Barrett formula was -0.35 ± 1.0 D. Higher axial length (≥25.5 mm) was associated with greater prediction error (-0.72 ± 1.11 D vs -0.18 ± 0.91 D, P = .048). Twelve re-subluxations occurred over a mean follow-up period of 30.28 ± 41.86 months. The predicted 50% survival of iris-sutured lenses was 114.25 months., Conclusions and Relevance: Iris-suture fixation may require moderate lens power adjustment to compensate for prediction error, especially in eyes with higher axial length. Longer follow-up demonstrates that iris-suture fixation remains a viable technique, yet re-subluxations require routine monitoring of such eyes., (© 2020 Royal Australian and New Zealand College of Ophthalmologists.)

Purpose: This study aims to map force interaction between instrument and sclera of in vivo rabbits during retinal procedures, and verify if a robotic active force control could prevent unwanted increase of forces on the sclera., Methods: Experiments consisted in the performance of intraocular movements of a force sensing instrument, adjacent to the retinal surface, in radial directions, from the center to the periphery and back, and compared manual manipulations with robotic assistance and also robotic assistance with an active force control. This protocol was approved by the Animal Use and Ethical Committee and experiments were according to ARVO Statement of Animal Use., Results: Mean forces using manual manipulations were 115 ± 51 mN. Using robotic assistance, mean forces were 118 ± 49 mN. Using an active force control method, overall mean forces reduced to 69 ± 15, with a statistical difference compared with other methods ( P < 0.001). Comparing intraocular directions, superior sector required higher forces and the force control method reduced differences in forces between users and retained the same force pattern between them., Conclusions: Results validate that the introduction of robotic assistance might increase the dynamic interactions between instrument and sclera, and the addition of an active force control method reduces the forces at levels lower than manual manipulations., Translational Relevance: All marketing benefits from extreme accuracy and stability from robots, however, redundancy of safety mechanisms during intraocular manipulations, especially on force control and surgical awareness, would allow all utility of robotic assistance in ophthalmology., Competing Interests: Disclosure: M.G. Urias, None; N. Patel, None; A. Ebrahimi, None; I, Iordachita, None; P.L. Gehlbach, None, (Copyright 2020 The Authors.)

Importance: Vitreoretinal surgery can be technically challenging and is limited by physiologic characteristics of the surgeon. Factors that improve accuracy and precision of the vitreoretinal surgeon are invaluable to surgical performance., Objectives: To establish weight-adjusted cutoffs for caffeine and β-blocker (propranolol) intake and to determine their interactions in association with the performance of novice vitreoretinal microsurgeons., Design, Settings, and Participants: This single-blind cross-sectional study of 15 vitreoretinal surgeons who had less than 2 years of surgical experience was conducted from September 19, 2018, to September 25, 2019, at a dry-laboratory setting. Five simulations were performed daily for 2 days. On day 1, performance was assessed after sequential exposure to placebo, low-dose caffeine (2.5 mg/kg), high-dose caffeine (5.0 mg/kg), and high-dose propranolol (0.6 mg/kg). On day 2, performance was assessed after sequential exposure to placebo, low-dose propranolol (0.2 mg/kg), high-dose propranolol (0.6 mg/kg), and high-dose caffeine (5.0 mg/kg)., Interventions: Surgical simulation tasks were repeated 30 minutes after masked ingestion of placebo, caffeine, or propranolol pills during the 2 days., Main Outcomes and Measures: An Eyesi surgical simulator was used to assess surgical performance, which included surgical score (range, 0 [worst] to 700 [best]), task completion time, intraocular trajectory, and tremor rate (range, 0 [worst] to 100 [best]). The nonparametric Friedman test followed by Dunn-Bonferroni post hoc test was applied for multiple comparisons., Results: Of 15 vitreoretinal surgeons, 9 (60%) were male, with a mean (SD) age of 29.6 (1.4) years and mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) of 23.15 (2.9). Compared with low-dose propranolol, low-dose caffeine was associated with a worse total surgical score (557.0 vs 617.0; difference, -53.0; 95% CI, -99.3 to -6.7; P = .009), a lower antitremor maneuver score (55.0 vs 75.0; difference, -12.0; 95% CI, -21.2 to -2.8; P = .009), longer intraocular trajectory (2298.6 vs 2080.7 mm; difference, 179.3 mm; 95% CI, 1.2-357.3 mm; P = .048), and increased task completion time (14.9 minutes vs 12.7 minutes; difference, 2.3 minutes; 95% CI, 0.8-3.8 minutes; P = .048). Postcaffeine treatment with propranolol was associated with performance improvement; however, surgical performance remained inferior compared with low-dose propranolol alone for total surgical score (570.0 vs 617.0; difference, -51.0; 95% CI, -77.6 to -24.4; P = .01), tremor-specific score (50.0 vs 75.0; difference, -16.0; 95% CI, -31.8 to -0.2; P = .03), and intraocular trajectory (2265.9 mm vs 2080.7 mm; difference, 166.8 mm; 95% CI, 64.1-269.6 mm; P = .03)., Conclusions and Relevance: The findings suggest that performance of novice vitreoretinal surgeons was worse after receiving low-dose caffeine alone but improved after receiving low-dose propranolol alone. Their performance after receiving propranolol alone was better than after the combination of propranolol and caffeine. These results may be helpful for novice vitreoretinal surgeons to improve microsurgical performance.

Retinal vein occlusion (RVO) is a vision threatening condition occurring in the central or the branch retinal veins. Risk factors include but are not limited to hypercoagulability, thrombus or other cause of low blood flow. Current clinically proven treatment options limit complications of vein occlusion without treating the causative occlusion. In recent years, a more direct approach called Retinal Vein Cannulation (RVC) has been explored both in animal and human eye models. Though RVC has demonstrated potential efficacy, it remains a challenging and risky procedure that demands precise needle manipulation to achieve safely. During RVC, a thin cannula (diameter 70-110 µm) is delicately inserted into a retinal vein. Its intraluminal position is maintained for up to 2 minutes while infusion of a therapeutic drug occurs. Because the tool-tissue interaction forces at the needle tip are well below human tactile perception, a robotic assistant combined with a force sensing microneedle could alleviate the challenges of RVC. In this paper we present a comparative study of manual and robot assisted retinal vein cannulation in chicken chorioallantoic membrane (CAM) using a force sensing microneedle tool. The results indicate that the average puncture force and average force during the infusion period are larger in manual mode than in robot assisted mode. Moreover, retinal vein cannulation was more stable during infusion, in robot assisted mode.

High-resolution real-time intraocular imaging of retina at the cellular level is very challenging due to the vulnerable and confined space within the eyeball as well as the limited availability of appropriate modalities. A probe-based confocal laser endomicroscopy (pCLE) system, can be a potential imaging modality for improved diagnosis. The ability to visualize the retina at the cellular level could provide information that may predict surgical outcomes. The adoption of intraocular pCLE scanning is currently limited due to the narrow field of view and the micron-scale range of focus. In the absence of motion compensation, physiological tremors of the surgeons' hand and patient movements also contribute to the deterioration of the image quality. Therefore, an image-based hybrid control strategy is proposed to mitigate the above challenges. The proposed hybrid control strategy enables a shared control of the pCLE probe between surgeons and robots to scan the retina precisely, with the absence of hand tremors and with the advantages of an image-based auto-focus algorithm that optimizes the quality of pCLE images. The hybrid control strategy is deployed on two frameworks - cooperative and teleoperated. Better image quality, smoother motion, and reduced workload are all achieved in a statistically significant manner with the hybrid control frameworks.

Eye surgery, specifically retinal micro-surgery involves sensory and motor skill that approaches human boundaries and physiological limits for steadiness, accuracy, and the ability to detect the small forces involved. Despite assumptions as to the benefit of robots in surgery and also despite great development effort, numerous challenges to the full development and adoption of robotic assistance in surgical ophthalmology, remain. Historically, the first in-human-robot-assisted retinal surgery occurred nearly 30 years after the first experimental papers on the subject. Similarly, artificial intelligence emerged decades ago and it is only now being more fully realized in ophthalmology. The delay between conception and application has in part been due to the necessary technological advances required to implement new processing strategies. Chief among these has been the better matched processing power of specialty graphics processing units for machine learning. Transcending the classic concept of robots performing repetitive tasks, artificial intelligence and machine learning are related concepts that has proven their abilities to design concepts and solve problems. The implication of such abilities being that future machines may further intrude on the domain of heretofore "human-reserved" tasks. Although the potential of artificial intelligence/machine learning is profound, present marketing promises and hype exceeds its stage of development, analogous to the seventieth century mathematical "boom" with algebra. Nevertheless robotic systems augmented by machine learning may eventually improve robot-assisted retinal surgery and could potentially transform the discipline. This commentary analyzes advances in retinal robotic surgery, its current drawbacks and limitations, and the potential role of artificial intelligence in robotic retinal surgery., Competing Interests: Competing interestsThe work of M. Urias was supported by the Instituto da Visão (IPEPO) and Lemann Foundation. The work of PLG was supported in part by Research to Prevent Blindness, New York, USA, and gifts by the J. Willard and Alice S. Marriott Foundation, the Gale Trust, Mr. Herb Ehlers, Mr. Bill Wilbur, Mr. and Mrs. Rajandre Shaw, Ms. Helen Nassif, Ms. Mary Ellen Keck, and Mr. Ronald Stiff., (© The Author(s) 2019.)

In this paper, a novel semi-autonomous control framework is presented for enabling probe-based confocal laser endomicroscopy (pCLE) scan of the retinal tissue. With pCLE, retinal layers such as nerve fiber layer (NFL) and retinal ganglion cell (RGC) can be scanned and characterized in real-time for an improved diagnosis and surgical outcome prediction. However, the limited field of view of the pCLE system and the micron-scale optimal focus distance of the probe, which are in the order of physiological hand tremor, act as barriers to successful manual scan of retinal tissue. Therefore, a novel sensorless framework is proposed for real-time semi-autonomous endomicroscopy scanning during retinal surgery. The framework consists of the Steady-Hand Eye Robot (SHER) integrated with a pCLE system, where the motion of the probe is controlled semi-autonomously. Through a hybrid motion control strategy, the system autonomously controls the confocal probe to optimize the sharpness and quality of the pCLE images, while providing the surgeon with the ability to scan the tissue in a tremor-free manner. Effectiveness of the proposed architecture is validated through experimental evaluations as well as a user study involving 9 participants. It is shown through statistical analyses that the proposed framework can reduce the work load experienced by the users in a statistically-significant manner, while also enhancing their performance in retaining pCLE images with optimized quality.

Pars plana vitrectomy is a challenging, minimally invasive microsurgical procedure due to its intrinsic manoeuvres and physiological limits that constrain human capability. An important human limitation is physiological hand tremor, which can significantly increase the risk of iatrogenic retinal damage resulting from unintentional manoeuvres that affect anatomical and functional surgical outcomes. The limitations imposed by normal physiological tremor are more evident and challenging during 'micron-scale' manoeuvres such as epiretinal membrane and internal limiting membrane peeling, and delicate procedures requiring coordinated bimanual surgery such as tractional retinal detachment repair. Therefore, over the previous three decades, attention has turned to robot-assisted surgical devices to overcome these challenges. Several systems have been developed to improve microsurgical accuracy by cancelling hand tremor and facilitating faster, safer and more effective microsurgeries. By markedly reducing tremor, microsurgical precision is improved to a level beyond present human capabilities. In conclusion, robotics offers potential advantages over free-hand microsurgery as it is currently performed during ophthalmic surgery and opens the door to a new class of revolutionary microsurgical modalities. The skills transfer that is beyond human capabilities to robotic technology is a logical next step in microsurgical evolution., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in patients over the age of 65 years in industrialized countries. Epidemiologic studies suggest that high dietary fat intake is a risk factor for the development and progression of both vascular and retinal disease. These, and other associations, suggest a hypothesis linking elevated cholesterol and AMD progression. It follows, therefore, that cholesterol-lowering medications, such as statins, may influence the onset and progression of AMD. However, the findings have been inconclusive as to whether statins play a role in AMD. Due to the significant public health implications of a potential inhibitory effect of statins on the onset and progression of AMD, it is important to continually evaluate emerging findings germane to this question.

The performance of retinal microsurgery often requires the coordinated use of both hands. During bimanual retinal surgery, dominant hand performance may be negatively impacted by poor non-dominant hand assistance. Therefore understanding bimanual latent determinants, and establishing safety criteria for bimanual manipulation is relevant to robotic development and to eventual patient care. In this paper, we present a preliminary study to quantitatively evaluate one aspect of bimanual tool use in retinal surgery. Two force sensing tools were designed and fabricated using fiber Bragg grating sensors. Tool-to-sclera contact force is measured using the developed tools and analyzed. The tool forces were recorded during five basic surgical maneuvers typical of retinal surgery. Two subjects are involved in experiments, including one clinician and one engineer. For comparison, all manipulations were replicated under robot-assisted conditions. The results indicate that the average tool-to-sclera force recorded from the dominant hand tool is significantly higher than that from the non-dominant hand tool ( p = 0.004). Moreover, the average forces under robot-assisted conditions with the present steady hand robot is notably higher than freehand conditions( p = 0.01). The forces obtained from the dominant and not-dominant hand instruments indicate a weak correlation.

Purpose: Posterior vitreous detachment (PVD) plays an important role in vitreoretinal interface disorders. Historically, observations of PVD using OCT have been limited to the macular region. The purpose of this study is to image the wide-angle vitreoretinal interface after PVD in normal subjects using montaged OCT images., Design: An observational cross-sectional study., Participants: A total of 144 healthy eyes of 98 normal subjects aged 21 to 95 years (51.4±22.0 [mean ± standard deviation])., Methods: Montaged images of horizontal and vertical OCT scans through the fovea were obtained in each subject., Main Outcome Measures: Montaged OCT images., Results: By using wide-angle OCT, we imaged the vitreoretinal interface from the macula to the periphery. PVD was classified into 5 stages: stage 0, no PVD (2 eyes, both aged 21 years); stage 1, peripheral PVD limited to paramacular to peripheral zones (88 eyes, mean age 38.9±16.2 years, mean ± standard deviation); stage 2, perifoveal PVD extending to the periphery (12 eyes, mean age 67.9±8.4 years); stage 3, peripapillary PVD with persistent vitreopapillary adhesion alone (7 eyes, mean age 70.9±11.9 years); stage 4, complete PVD (35 eyes, mean age 75.1±10.1 years). All stage 1 PVDs (100%) were observed in the paramacular to peripheral region where the vitreous gel adheres directly to the cortical vitreous and retinal surface. After progression to stage 2 PVD, the area of PVD extends posteriorly to the perifovea and anteriorly to the periphery. Vitreoschisis was observed in 41.2% at PVD initiation (stage 1a)., Conclusions: Whereas prior work suggests that PVD originates in the perifoveal region and after the sixth decade, our observations demonstrate that (1) PVD first appears even in the third decade of life and gradually appears more extensively throughout life; (2) more than 40% of eyes without fundus diseases at their PVD initiation are associated with vitreoschisis; and (3) PVD is first noted primarily in the paramacular-peripheral region where vitreous gel adheres to the retinal surface and is noted to be more extensive in older ages to ultimately involve the fovea., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Retinal microsurgery is technically demanding and requires high surgical skill with very little room for manipulation error. The introduction of robotic assistance has the potential to enhance and expand a surgeon's manipulation capabilities during retinal surgery, i.e., improve precision, cancel physiological hand tremor, and provide sensing information. However, surgeon performance may also be negatively impacted by robotic assistance due to robot structural stiffness and nonintuitive controls. In complying with robotic constraints, the surgeon loses the dexterity of the human hand. In this paper, we present a preliminary experimental study to evaluate user behavior when affected by robotic assistance during mock retinal surgery. In these experiments user behavior is characterized by measuring the forces applied by the user to the sclera, the tool insertion/retraction speed, the tool insertion depth relative to the scleral entry point, and the duration of surgery. The users' behavior data is collected during three mock retinal surgery tasks with four users. Each task is conducted using both freehand and robot-assisted techniques. The univariate user behavior and the correlations of multiple parameters of user behavior are analyzed. The results show that robot assistance prolongs the duration of the surgery and increases the manipulation forces applied to sclera, but refines the insertion velocity and eliminates hand tremor.

Vitreoretinal microsurgery is among the most technically challenging of the minimally invasive surgical techniques. Exceptional precision is required to operate on micron scale targets presented by the retina while also maneuvering in a tightly constrained and fragile workspace. These challenges are compounded by inherent limitations of the unassisted human hand with regard to dexterity, tremor and precision in positioning instruments. The limited human ability to visually resolve targets on the single-digit micron scale is a further limitation. The inherent attributes of robotic approaches therefore, provide logical, strategic and promising solutions to the numerous challenges associated with retinal microsurgery. Robotic retinal surgery is a rapidly emerging technology that has witnessed an exponential growth in capabilities and applications over the last decade. There is now a worldwide movement toward evaluating robotic systems in an expanding number of clinical applications. Coincident with this expanding application is growth in the number of laboratories committed to "robotic medicine". Recent technological advances in conventional retina surgery have also led to tremendous progress in the surgeon's capabilities, enhanced outcomes, a reduction of patient discomfort, limited hospitalization and improved safety. The emergence of robotic technology into this rapidly advancing domain is expected to further enhance important aspects of the retinal surgery experience for the patients, surgeons and society., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

In this study, we built and tested a handheld motion-guided micro-forceps system using common-path swept source optical coherence tomography (CP-SSOCT) for highly accurate depth controlled epiretinal membranectomy. A touch sensor and two motors were used in the forceps design to minimize the inherent motion artifact while squeezing the tool handle to actuate the tool and grasp, and to independently control the depth of the tool-tip. A smart motion monitoring and a guiding algorithm were devised to provide precise and intuitive freehand control. We compared the involuntary tool-tip motion occurring while grasping with a standard manual micro-forceps and our touch sensor activated micro-forceps. The results showed that our touch-sensor-based and motor-actuated tool can significantly attenuate the motion artifact during grasping (119.81 μm with our device versus 330.73 μm with the standard micro-forceps). By activating the CP-SSOCT based depth locking feature, the erroneous tool-tip motion can be further reduced down to 5.11μm. We evaluated the performance of our device in comparison to the standard instrument in terms of the elapsed time, the number of grasping attempts, and the maximum depth of damage created on the substrate surface while trying to pick up small pieces of fibers (Ø 125 μm) from a soft polymer surface. The results indicate that all metrics were significantly improved when using our device; of note, the average elapsed time, the number of grasping attempts, and the maximum depth of damage were reduced by 25%, 31%, and 75%, respectively.

Bimanual surgery enhances surgical effectiveness and is required to successfully accomplish complex microsurgical tasks. The essential advantage is the ability to simultaneously grasp tissue with one hand to provide counter traction or exposure, while dissecting with the other. Towards enhancing the precision and safety of bimanual microsurgery we present a bimanual SMART micro-surgical system for a preliminary ex-vivo study. To the best of our knowledge, this is the first demonstration of a handheld bimanual microsurgical system. The essential components include a ball-lens coupled common-path swept source optical coherence tomography sensor. This system effectively suppresses asynchronous hand tremor using two PZT motors in feedback control loop and efficiently assists ambidextrous tasks. It allows precise bimanual dissection of biological tissues with a reduction in operating time as compared to the same tasks performed with conventional one-handed approaches.

In microsurgery, the physiological hand tremor of the surgeon remains an important factor affecting procedure efficiency, risk of complications, and ultimately, the efficacy of treatment. The micro-scissors are routinely employed to perform precise sharp dissection of delicate tissues. Here, we present a dual optical coherence tomography (OCT) distance sensor guided, two-motor, horizontal smart micromanipulation aided robotic-surgery tool (SMART) micro-scissors. It is intended to improve surgeon performance by retaining all of the attributes of the horizontal scissors while implementing proof-of-concept use of two functional motors to provide tremor cancellation.

We propose, test and validate a novel Fourier-domain based method for ghost image artifacts reduction in a common-path SSOCT system having multiple adjacent reference planes. Common-path probes with imaging systems containing high-index sapphire ball or other lenses produce multiple fixed references due to Fresnel reflections from the lens surfaces. The multiple reference planes produce multiple and overlapping OCT images. Since such ghost artifacts are the result of the superposition of multiple identical images having different amplitudes and spatial shifts, one can correctly shift and sum the images in the Fourier-domain once the relative amplitude and lateral position between the reference planes are known. This theory and numerical testing are presented to elucidate our method. We then validate the potential effectiveness using OCT imaging experiments.

Purpose: To present baseline images of the vitreous, retina, and choroid from the macula to the periphery in normal patients using a novel montaging technique of spectral domain optical coherence tomography., Methods: Twenty-six normal eyes of 22 healthy volunteers were enrolled in this study. Montaged images of four radial optical coherence tomography scans through the fovea were obtained from each subject., Results: In the macula, there were six identifiable retinal layers as well as four bands in the outer retina. In the periphery, the ganglion cell layer was not identifiable. The external limiting membrane, the second band, and the retinal pigment epithelium were continuously delineated from the macula to the periphery. The third band was not visible in the periphery., Conclusion: Spectral domain optical coherence tomography montaged images provide wide-angle images of the vitreous, retina, and choroid, allowing for evaluation of peripheral findings and examination of relationships between peripheral and posterior disease. The maximum scan length achieved here was 36 mm. The scan length is approximately three times than that provided by conventional posterior scanning and is consistent with known dimensions of the eye. This method is achievable with current commercially available devices and may contribute to decision making in clinical practice.

Importance: We have developed a novel surgical technique, to our knowledge, for the management of subluxated crystalline lenses involving preplacement of an iris-sutured posterior chamber intraocular lens (PCIOL) before pars plana vitrectomy and lensectomy., Objective: To investigate the outcomes of eyes with subluxated crystalline lenses, predominantly a result of Marfan syndrome (14 eyes [58%]) or trauma (5 eyes [21%]), that underwent pars plana vitrectomy and lensectomy with placement of an iris-sutured PCIOL., Design, Setting, and Participants: We performed a retrospective, noncomparative case series of 24 eyes from 17 consecutive adult patients with surgically treated subluxated crystalline lenses presenting to the Wilmer Eye Institute at Johns Hopkins Hospital from October 6, 2006, through May 1, 2013. The mean (SD) postoperative follow-up was 24.4 (20.5) months for eyes with at least 6 months of follow-up (last date, October 13, 2014). We performed the analysis from January 21, 2014, through January 3, 2015., Main Outcomes and Measures: Improvement in best-corrected visual acuity using an automated Snellen chart and induction of astigmatism for eyes with at least 6 months of follow-up (n = 18) and IOL stability during follow-up for all eyes (n = 24)., Results: The mean (SD) age at surgery was 49.4 (10.7 [range, 29-67]) years. We found an improvement in mean (SD [95% CI]) best-corrected visual acuity from 0.66 (0.71 [0.30-1.02]) logMAR preoperatively (Snellen equivalent, approximately 20/90; range, 20/30 to hand motions) to 0.07 (0.11 [95% CI, 0.01-0.12]) logMAR postoperatively (Snellen equivalent, approximately 20/23; range, 20/15 to 20/50). We found little change in astigmatism postoperatively (mean change, -0.1 [95% CI, -0.5 to 0.13] diopters). Postoperative complications included retinal detachment (1 eye [4%]), retained cortical fragment (1 [4%]), cystoid macular edema (2 [8%]), and IOL subluxation (3 [13%]) owing to haptic slippage within 3 months of the procedure. The overall probability of successfully achieving placement of a centered iris-sutured PCIOL in patients with follow-up of longer than 6 months (n = 18) was 100% (95% CI, 81.5%-100%)., Conclusions and Relevance: Placement of iris-sutured PCIOLs at the time of subluxated lens extraction with a pars plana surgical approach yields favorable results in terms of postoperative visual outcomes and surgical complications. This technique offers an effective procedure for surgeons to use when treating clinically significant subluxated crystalline lenses.

Purpose: To describe the outcomes of combined pars plana vitrectomy (PPV) and iris suture fixation of posteriorly dislocated intraocular lenses (IOLs)., Setting: Tertiary academic referral center., Design: Retrospective noncomparative consecutive case series., Methods: The included eyes had posteriorly dislocated IOLs and had combined PPV and iris suture fixation. The IOL dislocations amenable to surgical repair with an anterior approach were excluded. Outcome measures included improvement in corrected distance visual acuity (CDVA), induction of astigmatism, and complications., Results: This study consisted of 27 consecutive cases. The mean follow-up was 6.61 months ± 8.1 (SD). The median postoperative CDVA was 20/30, and 16 of 27 eyes had stable or improved CDVA compared with baseline; 8 of the others had a shift from aphakic to pseudophakic correction. Overall, a significant myopic shift in spherical equivalent occurred after surgery, from 7.62 ± 4.38 diopters (D) to -1.33 ± 1.45 D (P < .001). Surgically induced astigmatism (SIA) assessed by comparing the difference in preoperative keratometry readings with the difference in postoperative manifest refraction cylinder adjusted to the corneal plane gave the following: 1.89 ± 1.09 D versus 1.13 ± 0.86 D, respectively (P < .001). All IOLs were stable and centered at the last follow-up; however, 1 was mildly tilted. One eye had a recurrent subluxation, and the IOL was resutured before the end of the study. No cases of endophthalmitis or retinal detachment occurred., Conclusion: Combined PPV and iris suture fixation of posteriorly dislocated IOLs led to stable fixation of the IOLs., Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To demonstrate the posterior vitreous mobility following eye movements in patients forming macular holes, using an optical coherence tomography (OCT) eye-tracking system., Design: Prospective consecutive interventional case series., Methods: Twenty-four eyes of 17 consecutive patients with idiopathic macular hole and the remaining fellow eyes were recruited. Following acquisition of baseline fundus scans, all patients were instructed to perform sets of standardized full-excursion vertical and horizontal eye movements. Immediately after each set of movements an OCT scan registered to the baseline fundus image was obtained using the eye-tracking system. Three images were then overlaid using picture-editing software, thereby documenting the changing configuration of the posterior vitreous as well as its position relative to the static retinal structures., Results: In patients with macular hole, 22 of 24 eyes (92%) had duplication of the posterior cortical vitreous in overlaid images. The extent of duplication (indicating mobility) was increased with increasing vitreous separation and as the stage of macular hole increased (75% in stage 0; 80% in stage 1; 100% in both stage 2 and stage 3). In all eyes in which there was a wavy configuration to the vitreous face, or in which there was a greater angle of vitreous insertion into the peripheral retina, vitreous mobility was evident on overlaid images (P = 2.7 × 10(-17) and P = 1.7 × 10(-13), respectively)., Conclusion: By dynamically evaluating patients, we offer potential mechanistic insights that may further implicate mobile vitreous and associated fluid currents in the pathogenesis and progression of macular holes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

This paper presents a novel intuitive targeting and tracking scheme that utilizes a common-path swept source optical coherence tomography (CP-SSOCT) distal sensor integrated handheld microsurgical tool. To achieve micron-order precision control, a reliable and accurate OCT distal sensing method is required; simultaneously, a prediction algorithm is necessary to compensate for the system delay associated with the computational, mechanical and electronic latencies. Due to the multi-layered structure of retina, it is necessary to develop effective surface detection methods rather than simple peak detection. To achieve this, a shifted cross-correlation method is applied for surface detection in order to increase robustness and accuracy in distal sensing. A predictor based on Kalman filter was implemented for more precise motion compensation. The performance was first evaluated using an established dry phantom consisting of stacked cellophane tape. This was followed by evaluation in an ex-vivo bovine retina model to assess system accuracy and precision. The results demonstrate highly accurate depth targeting with less than 5 μm RMSE depth locking.

Purpose: To identify predictors of visual outcomes following Boston type 1 Keratoprosthesis (KPro) implantation., Design: Retrospective chart review., Methods: Data regarding preoperative clinical and demographic characteristics and postoperative course were collected., Patients: Fifty-nine eyes of 59 adult patients who underwent KPro implantation between January 2006 and March 2012 at a single tertiary care center., Main Outcome Measures: Preoperative factors associated with all-cause and glaucoma-related loss of visual acuity from the best postoperative visual acuity noted., Results: Fifty-two of 59 eyes (88%) achieved improved vision post implantation, with 7 eyes failing to gain vision as a result of pre-existing glaucoma (n = 4) or retino-choroidal disease (n = 3). Twenty-one eyes (21/52, 40%) maintained their best-ever visual acuity at last visit (mean follow-up period was 37.8 months). The likelihood of maintaining best-ever vision was 71% at 1 year, 59% at 2 years, and 48% at 3 years. Primary KPro implantation was associated with a higher likelihood of losing best-ever vision as compared to KPro implantation as a repeat corneal procedure (hazard ratio [HR] = 3.06; P = 006). The main reasons for postimplantation vision loss was glaucoma (12/31, 39%), and the risk of glaucomatous visual acuity loss was 15% at 2 years and 27% at 3 years. Prior trabeculectomy was associated with a higher rate of vision loss from glaucoma (HR = 3.25, P = .04)., Conclusion: Glaucoma is the primary reason for loss of visual acuity after KPro implantation. Conditions necessitating primary KPro surgery are associated with more frequent all-cause vision loss. Prospective trials are necessary to better determine which clinical features best predict KPro success., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Manual micro-surgical tasks are fundamentally divided into grasping, cutting and injecting maneuvers performed on biological tissues. Efficient dissection of fibrous tissue from the surface of the retina often requires grasping and cutting maneuvers carried out simultaneously. True bimanual surgery requires that the surgeon contend with the innate hand tremor of two hands at once as well as unpredicted patient's movement. In this study, we develop and test a dual SMART micro-surgical system to suppress bimanual hand tremor during micro-surgical dissection.

Purpose: To evaluate localization and transgene expression from adenoviral vector of serotypes 5, 35, and 28, ± an RGD motif in the fiber following intravitreal or subretinal administration., Methods: Ocular transduction by adenoviral vector serotypes ± RGD was studied in the eyes of mice receiving an intravitreous or subretinal injection. Each serotype expressed a CMV-GFP expression cassette and histological sections of eyes were examined. Transgene expression levels were examined using luciferase (Luc) regulated by the CMV promoter., Results: GFP localization studies revealed that serotypes 5 and 28 given intravitreously transduced corneal endothelial, trabecular, and iris cells. Intravitreous delivery of the unmodified Ad35 serotype transduced only trabecular meshwork cells, but, the modification of the RGD motif into the fiber of the Ad35 viral vector base expanded transduction to corneal endothelial and iris cells. Incorporation of the RGD motif into the fiber knob with deletion of RGD from the penton base did not affect the transduction ability of the Ad5 vector base. Subretinal studies showed that RGD in the Ad5 knob shifted transduction from RPE cells to photoreceptor cells. Using a CMV-Luc expression cassette, intravitreous delivery of all the tested vectors, such as Ad5-, Ad35- and Ad28- resulted in an initial rapid induction of luciferase activity that thereafter declined. Subretinal administration of vectors showed a marked difference in transgene activity. Ad35-Luc gene expression peaked at 7 days and remained elevated for 6 months. Ad28-Luc expression was high after 1 day and remained sustained for one month., Conclusions: Different adenoviral vector serotypes ± modifications transduce different cells within the eye. Transgene expression can be brief or extended and is serotype and delivery route dependent. Thus, adenoviral vectors provide a versatile platform for the delivery of therapeutic agents for ocular diseases.

This paper presents a handheld micro-injector system using common-path swept source optical coherence tomography (CP-SSOCT) as a distal sensor with highly accurate injection-depth-locking. To achieve real-time, highly precise, and intuitive freehand control, the system used graphics processing unit (GPU) to process the oversampled OCT signal with high throughput and a smart customized motion monitoring control algorithm. A performance evaluation was conducted with 60-insertions and fluorescein dye injection tests to show how accurately the system can guide the needle and lock to the target depth. The evaluation tests show our system can guide the injection needle into the desired depth with 4.12 um average deviation error while injecting 50 nl of fluorescein dye.

A handheld Smart Micromanipulation Aided Robotic-surgery Tool (SMART) micro-forceps guided by a fiber-optic common-path optical coherence tomography (CP-OCT) sensor is presented. A fiber-optic CP-OCT distance and motion sensor is integrated into the shaft of a micro-forceps. The tool tip position is manipulated longitudinally through a closed loop control using a piezoelectric motor. This novel forceps design could significantly enhance safety, efficiency and surgical outcomes. The basic grasping and peeling functions of the micro-forceps are evaluated in dry phantoms and in a biological tissue model. As compared to freehand use, targeted grasping and peeling performance assisted by active tremor compensation, significantly improves micro-forceps user performance.

During freehand performance of vitreoretinal microsurgery the surgeon must perform precise and stable maneuvers that achieve surgical objectives and avoid surgical risk. Here, we present an improved smart handheld microsurgical tool which is based on a ball lens fiber optic sensor that utilizes common path swept source optical coherence tomography. Improvements include incorporation of a ball lens single mode fiber optic probe that increases the working angle of the tool to greater than 45 degrees; and increases the magnitude of the distance sensing signal through water. Also presented is a cutting function with an improved ergonomic design.

Purpose: To describe the morphologic and anatomic relationships at the vitreoretinal interface, from the macula into the periphery, in patients with idiopathic macular hole. Montaged images of posterior and peripheral spectral-domain (SD) optical coherence tomography (OCT) studies were used to describe the anatomic vitreoretinal relationships., Design: Prospective, consecutive, observational case series., Participants: Forty-six eyes of thirty-six consecutive patients with idiopathic macular hole and their fellow eyes., Methods: Montage images of 4 radial OCT scans (horizontal, vertical, and 2 oblique scans) through the fovea were obtained in each case., Main Outcome Measures: Montage SD OCT images., Results: In fellow eyes, potential precursor changes to macular hole revealed shallow perifoveal vitreous separation that extends peripherally toward the equator. Two distinct configurations were noted at the posterior vitreous face; eyes without holes had a smooth curvature, whereas eyes with holes were more likely to have wavy, folded, or scalloped vitreous surfaces. At the onset of separation, most posterior vitreous cortex had a smooth curvature, but posterior vitreous folds increased with progressive separation. Also notable were zones of double-layered retinoschisis in regions of adherent posterior vitreous. Resulting granular hyperreflection in the peripheral vitreous was detectable in 50% to 60% of stage 1 or 2 holes but in only 33% of stage 3 or 4 holes., Conclusions: The SD OCT montages taken at serial stages of idiopathic macular holes document distinct configurations of the posterior vitreous face, granular hyperreflection in the peripheral vitreous, and areas of peripheral retinoschisis. Montaging SD OCT images provides novel cross-sectional images of the vitreoretinal interface that may have broader application., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Microsurgeons require dexterity to make precise and stable maneuvers to achieve surgical objectives and to minimize surgical risks during freehand procedures. This work presents a novel, common path, swept source optical coherence tomography-based "smart" micromanipulation aided robotic-surgical tool (SMART) that actively suppresses surgeon hand tremor. The tool allows enhanced tool tip stabilization, more accurate targeting and the potential to lower surgical risk. Freehand performance is compared to smart tool-assisted performance and includes assessment of the one-dimensional motion tremor in an active microsurgeon's hand. Surgeon hand tremor-the ability to accurately locate a surgical target and maintain tool tip offset distances-were all improved by smart tool assistance.

We delivered adenovirus vector (Ad) via intravitreous injection and monitored transgene (luciferase) expression in living mice (BALB/c) at multiple time points. In vivo live imaging technology was able to assess dynamically intraocular luciferase expression in a single animal population throughout the entire experiment period. Using this information, we were able to determine the optimal time point for readministration of Ad into the eyes and to dynamically study the time course of expression of a second Ad administration. Optical imaging demonstrated the limited period of transgene expression in eyes. Significant transgene signal was also detected in livers. The repeat intraocular delivery of the adenovirus resulted in significant blunting of transgene expression in both eyes and livers compared to the initial delivery. Periocular corticosteroid (triamcinolone acetonide) injection combined with initial Ad delivery was effective to rescue luciferase expression on repeat Ad vector delivery. However, this effect was not observed when corticosteroid was combined with repeat Ad delivery. Although corticosteroid enhanced ocular transgene expression, it also increased transgene expression in liver, which has potential safety implications. This dynamic transgene expression in eyes was successfully traced and monitored via a live imaging technique.

The authors describe the development of an ultrafast three-dimensional (3D) optical coherence tomography (OCT) imaging system that provides real-time intraoperative video images of the surgical site to assist surgeons during microsurgical procedures. This system is based on a full-range complex conjugate free Fourier-domain OCT (FD-OCT). The system was built in a CPU-GPU heterogeneous computing architecture capable of video OCT image processing. The system displays at a maximum speed of 10 volume/s for an image volume size of 160 × 80 × 1024(X × Y × Z) pixels. We have used this system to visualize and guide two prototypical microsurgical maneuvers: microvascular anastomosis of the rat femoral artery and ultramicrovascular isolation of the retinal arterioles of the bovine retina. Our preliminary experiments using 3D-OCT-guided microvascular anastomosis showed optimal visualization of the rat femoral artery (diameter<0.8 mm), instruments, and suture material. Real-time intraoperative guidance helped facilitate precise suture placement due to optimized views of the vessel wall during anastomosis. Using the bovine retina as a model system, we have performed "ultra microvascular" feasibility studies by guiding handheld surgical micro-instruments to isolate retinal arterioles (diameter ~0.1 mm). Isolation of the microvessels was confirmed by successfully passing a suture beneath the vessel in the 3D imaging environment.