ASSESSMENT OF SIMULATED SURGICAL DEXTERITY AFTER MODIFIABLE EXTERNAL EXPOSURES AMONG NOVICE VERSUS EXPERIENCED VITREORETINAL SURGEONS.

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.

Prediction error in iris suture fixated intraocular lenses and long-term stability.

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.

Posterior Vitreous Detachment as Observed by Wide-Angle OCT Imaging.

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.

The Question of a Role for Statins in Age-Related Macular Degeneration.

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.

Motorized Micro-Forceps with Active Motion Guidance based on Common-Path SSOCT for Epiretinal Membranectomy.

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.

Dual optical coherence tomography sensor guided, two-motor, horizontal SMART micro-scissors.

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.

Ghost reduction in CP-SSOCT having multiple references using Fourier-domain Shift and Sum.

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.

RETINOCHOROIDAL MORPHOLOGY DESCRIBED BY WIDE-FIELD MONTAGE IMAGING OF SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

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.

Effects of fetal haemoglobin on systemic oxygenation in preterm infants and the development of retinopathy of prematurity PacIFiHER Report No. 2.

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 SpO2 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 SpO2, lower PCO2, lower FiO2 from birth to 31 weeks PMA and 31 to 34 weeks PMA (rs=0.51, rs=-0.62 and rs=-0.63; p<0.0001 and rs=0.71, rs=-0.58 and rs=-0.79; p<0.0001, respectively). To maintain oxygen saturation goals set by the neonatal intensive care unit, higher median FiO2 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; FiO2=35 (21-100) versus 21 (21-30) p<0.006 and FiO2=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 PCO2, 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. O2 saturation goals to prevent ROP may need to incorporate relative amount of HbF.

A Polysomnographic Study of Effects of Sleep Deprivation on Novice and Senior Surgeons during Simulated Vitreoretinal Surgery.

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.

Viral transgene expression delivered by repeat intraocular adenoviral vector injection: in vivo live imaging study.

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.

Montage images of spectral-domain optical coherence tomography in eyes with idiopathic macular holes.

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.

Active tremor cancellation by a "smart" handheld vitreoretinal microsurgical tool using swept source optical coherence tomography.

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.

Mechanistic Insights into the Pathogenesis of Proliferative and Nonproliferative Vitreomacular Traction.

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.

Associations of cigarette smoking but not serum fatty acids with age-related macular degeneration in a Japanese population.

PURPOSE: To assess modifiable environmental risk factors and protective factors for age-related macular degeneration (AMD) in a native Japanese population. DESIGN: A case-control study. PARTICIPANTS: We included 422 case-control samples composed of 279 consecutive AMD cases and 143 controls. METHODS: Information regarding systemic conditions and lifestyle were documented in each subject by standardized questionnaire including age, gender, smoking history, body mass index (BMI), and history of cardiovascular disease, hypertension, and diabetes. Serum fatty acids profiles were analyzed by gas chromatography performed on blood samples taken from each study participant. Logistic regression and multiple comparison analyses were utilized in this study. MAIN OUTCOME MEASURES: Population-specific information assessing systemic conditions, lifestyle, and serum fatty acid profiles. RESULTS: Among environmental factors analyzed cigarette smoking showed the most significant association with development of all AMD (P<0.00001; odds ratio [OR], 4.06; 95% confidence interval [CI], 2.22-7.43), typical neovascular AMD (P<0.0001, OR, 4.59; 95% CI, 2.29-9.18), and polypoidal choroidal vasculopathy (P<0.001; OR, 4.87; 95% CI, 1.96-12.1). Hypertension and BMI showed a mild association with AMD. Although male prevalence was significantly higher in all case groups than in controls with conventional Scheffe correction, there was no association of gender with AMD development when logistic regression analysis was used to adjust for cigarette smoking. There was no difference in fatty acid profiles, except for a mild association of eicosapentaenoic acid concentration in the all AMD group. CONCLUSIONS: In the Japanese population studied, cigarette smoking influenced the risk of AMD but fractionated serum fatty acid levels did not. Although prior reports indicate a male predominance in Japanese patients with AMD, this study demonstrates that cigarette smoking accounts for this confounding bias. In addition, our population-specific data do not demonstrate significant differences in serum fatty acid composition, including ω-3 and ω-6 long chain polyunsaturated fatty acids, in Japanese patients with and without AMD. These results are consistent with the high proportion of smokers in aged Japanese men and the high fish oil intake in this population. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Complement factor H and high-temperature requirement A-1 genotypes and treatment response of age-related macular degeneration.

PURPOSE: To determine whether there is an association between complement factor H (CFH), high-temperature requirement A-1 (HTRA1), vascular endothelial growth factor (VEGF), and pigment epithelium-derived factor (PEDF) genotypes and response to treatment with photodynamic therapy (PDT) for age-related macular degeneration (AMD) in a Japanese population. DESIGN: Prospective, case-control study. PARTICIPANTS: One hundred ten patients with exudative AMD treated by verteporfin PDT were recruited prospectively at the Department of Ophthalmology, Saitama Medical University Hospital, Saitama, Japan. METHODS: The patients were genotyped for 4 single nucleotide polymorphisms (SNPs; rs800292, rs1061170, rs1410996, rs2274700) in the CFH gene, a rs11200638-SNP in the HTRA1 gene, 3 SNPs (rs699947, rs1570360, rs2010963) in the VEGF gene, and 4 SNPs (rs12150053, rs12948385, rs9913583, rs1136287) in the PEDF gene using a TaqMan assay. MAIN OUTCOME MEASURES: The treatment outcomes and genotypes of CFH, HTRA1, VEGF, and PEDF polymorphisms. RESULTS: Best-corrected visual acuity 1 year after PDT was significantly increased in patients with the HTRA1-rs11200638 GG genotype as compared with patients with the GA or AA genotypes (P = 2.9 × 10⁻², 7.0 × 10⁻4, respectively). The rate of recurrence in the 12-month period after PDT was also associated with HTRA1-rs11200638 genotype (P = 3.12 × 10⁻²). Patients with the AA genotype of HTRA1-rs11200638 had an approximately 6-fold greater risk of the recurrence than patients with the GG genotype (P = 5.58 × 10⁻³). Significant differences were demonstrated in the mean time interval from the initial treatment to the time of recurrence for the genotypes of CFH-rs1410996/-rs2274700 (P = 8.50 × 10⁻³). CONCLUSIONS: The HTRA1-rs11200638 and CFH-rs1410996/-rs2274700 variants were associated with response to PDT in this study population. These variants may be used for genetic biomarkers to estimate visual outcomes and recurrences in the response to PDT with significant predictive power.

Current and novel multi-imaging modalities to assess retinal oxygenation and blood flow.

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.

Posterior Vitreous Detachment in Normal Healthy Subjects Younger Than Age Twenty.

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.

Phenotype and genotype characteristics of age-related macular degeneration in a Japanese population.

PURPOSE: To describe phenotype and genotype characteristics of age-related macular degeneration (AMD) in Japanese patients. DESIGN: A case-control study. PARTICIPANTS: A total of 550 case-control samples composed of 408 consecutive AMD cases and 142 controls. METHODS: Clinical information assessing age, gender, affected eyes, fundus features, and fluorescein/indocyanine green angiograms were systematically evaluated. Four single nucleotide polymorphisms (SNPs; rs800292, rs1061170, rs1410996, rs2274700) in the complement factor H (CFH) gene, 1 SNP (rs11200638) in the high-temperature requirement factor A1 (HTRA1) gene, 3 SNPs (rs699947, rs1570360, rs2010963) in the vascular endothelial growth factor (VEGF) gene, and 4 SNPs (rs12150053, rs12948385, rs9913583, rs1136287) in the pigment epithelium-derived factor (PEDF) gene were assessed using TaqMan technology. MAIN OUTCOME MEASURES: The clinical phenotype information and genotypes of CFH, HTRA1, VEGF, and PEDF polymorphisms. RESULTS: Of Japanese patients with neovascular AMD (nAMD), 219 (58.7%) had typical nAMD and 154 (41.3%) had polypoidal choroidal vasculopathy (PCV). The frequency of bilateral exudative involvement was similar between typical nAMD (15.5%) and PCV (13.6%) (P = 0.613). Significant soft drusen were observed in the fellow eyes of 88 (47.6%) of 185 patients with unilateral typical nAMD and in 25 (18.8%) of 133 patients with unilateral PCV (P = 1.24x10(-7)). A serous pigment epithelium detachment was seen in 55 (25.1%) of 219 patients with typical nAMD and in 64 (41.6%) of 154 patients with PCV. A significant association was noted in CFH-rs800292, CFH-rs1410996, CFH-rs2274700, and HTRA1-rs11200638 with AMD development (P = 2.36x10(-5), 7.18x10(-5), 7.18x10(-5), 2.70x10(-7), respectively; population attributable risk = 57.3%, 57.8%, 57.8%, and 58.9%, respectively). We estimated the highest-risk group to have an approximately 70-fold greater risk of nAMD compared with the lowest-risk group when analyzing a combination of 4 SNPs in the CFH and HTRA1 genes. CONCLUSIONS: The Japanese AMD phenotype is characterized by a higher frequency of PCV, male predominance, and lower frequency of bilateral presentation compared with Caucasian AMD. Genotype analyses demonstrate a significant population attributable risk for SNPs in the CFH and HTRA1 genes and demonstrate joint effects for both genes. Gene variants in both CFH and HTRA1 contribute significantly to the AMD phenotype in a Japanese population.

A Comparison of Manual and Robot Assisted Retinal Vein Cannulation in Chicken Chorioallantoic Membrane.

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.