Publications by authors named "Marina Roizenblatt"

23 Publications

  • Page 1 of 1

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

Br J Ophthalmol 2021 Oct 7. Epub 2021 Oct 7.

Retina, Johns Hopkins Wilmer Eye Institute, Baltimore, Maryland, USA.

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 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, lower PCO, lower FiO from birth to 31 weeks PMA and 31 to 34 weeks PMA (r=0.51, r=-0.62 and r=-0.63; p<0.0001 and r=0.71, r=-0.58 and r=-0.79; p<0.0001, respectively). To maintain oxygen saturation goals set by the neonatal intensive care unit, higher median FiO 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=35 (21-100) versus 21 (21-30) p<0.006 and FiO=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, 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 saturation goals to prevent ROP may need to incorporate relative amount of HbF.
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http://dx.doi.org/10.1136/bjophthalmol-2021-319546DOI Listing
October 2021

A MULTIFACTORIAL APPROACH FOR IMPROVING THE SURGICAL PERFORMANCE OF NOVICE VITREORETINAL SURGEONS.

Retina 2021 Oct;41(10):2163-2171

Department of Ophthalmology, Universidade Federal de São Paulo, São Paulo, Brazil.

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.
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http://dx.doi.org/10.1097/IAE.0000000000003147DOI Listing
October 2021

Auditory Feedback Effectiveness for Enabling Safe Sclera Force in Robot-Assisted Vitreoretinal Surgery: a Multi-User Study.

Rep U S 2020 Oct 10;2020. Epub 2021 Feb 10.

Mechanical Engineering Department and Laboratory for Computational Sensing and Robotics (LCSR) at the Johns Hopkins University, Baltimore, MD, 21218, USA.

Robot-assisted retinal surgery has become increasingly prevalent in recent years in part due to the potential for robots to help surgeons improve the safety of an immensely delicate and difficult set of tasks. The integration of robots into retinal surgery has resulted in diminished surgeon perception of tool-to-tissue interaction forces due to robot's stiffness. The tactile perception of these interaction forces (sclera force) has long been a crucial source of feedback for surgeons who rely on them to guide surgical maneuvers and to prevent damaging forces from being applied to the eye. This problem is exacerbated when there are unfavorable sclera forces originating from patient movements (dynamic eyeball manipulation) during surgery which may cause the sclera forces to increase even drastically. In this study we aim at evaluating the efficacy of providing warning auditory feedback based on the level of sclera force measured by force sensing instruments. The intent is to enhance safety during dynamic eye manipulations in robot-assisted retinal surgery. The disturbances caused by lateral movement of patient's head are simulated using a piezo-actuated linear stage. The Johns Hopkins Steady-Hand Eye Robot (SHER), is then used in a multi-user experiment. Twelve participants are asked to perform a mock retinal surgery by following painted vessels inside an eye phantom using a force sensing instrument while auditory feedback is provided. The results indicate that the users are able to handle the eye motion disturbances while maintaining the sclera forces within safe boundaries when audio feedback is provided.
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http://dx.doi.org/10.1109/iros45743.2020.9341350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321408PMC
October 2020

Studies of Microsurgical Skill-The Key Lies in the Design-Reply.

JAMA Ophthalmol 2021 01;139(1):127-128

Department of Ophthalmology, Universidade Federal de São Paulo, São Paulo, Brazil.

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http://dx.doi.org/10.1001/jamaophthalmol.2020.4758DOI Listing
January 2021

Effect of chronic cocaine use on fine motor coordination tested during ophthalmic vitreoretinal simulated performance.

J Psychiatr Res 2021 01 30;132:7-12. Epub 2020 Sep 30.

Department of Ophthalmology, Universidade Federal de São Paulo, 821, Botucatu Street, 1st floor, 04023-062, Administrative Office, São Paulo, Brazil; Vision Institute, IPEPO, Paulista Medical School, 1083, 11 floor, Borges Lagoa Street, 04038-032, Administrative Office, São Paulo, Brazil. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jpsychires.2020.09.032DOI Listing
January 2021

Association of Weight-Adjusted Caffeine and β-Blocker Use With Ophthalmology Fellow Performance During Simulated Vitreoretinal Microsurgery.

JAMA Ophthalmol 2020 08;138(8):819-825

Department of Ophthalmology, Universidade Federal de São Paulo, São Paulo, Brazil.

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.
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http://dx.doi.org/10.1001/jamaophthalmol.2020.1971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290718PMC
August 2020

Lower foetal haemoglobin levels at 31- and 34-weeks post menstrual age is associated with the development of retinopathy of prematurity : PacIFiHER Report No. 1 PacIFiHER Study Group (Preterm Infants and Fetal Haemoglobin in ROP).

Eye (Lond) 2021 02 14;35(2):659-664. Epub 2020 May 14.

Retina Division, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background/objectives: Previous studies have suggested that lower mean foetal haemoglobin (HbF) levels is associated with an increased risk for developing retinopathy of prematurity (ROP). Lower HbF levels may lead to high oxygen exposure to the developing retina thereby increasing the risk of acute ROP. In this study, we characterize the temporal relationship of HbF levels and the development of ROP.

Subjects/methods: This is a single institution prospective observational cohort study. Preterm infants (born <31 weeks gestational age or <1500 g) with HbF measured at birth (cord blood), 31-, 34-, and 37-weeks post menstrual age (PMA); and at least one ROP exam, were enrolled.

Results: A total of 60 preterm infants (28 females, 47%) were enrolled. At 31-, 34-, 37-weeks PMA, infants with ROP (mild = Type 2 or less severe and severe = Type 1 ROP) had statistically lower percentages of HbF than infants with no ROP (28.2 ± 15 and 9.7 ± 2.9 vs 67.1 ± 29.6; p < 0.0001; 23.3 ± 14.7 and 32.5 vs 60.1 ± 25; p < 0.005; 31.9 ± 15.8 and 41.6 vs 60.2 ± 20.0; p < 0.0019). Infants with HbF levels in the lowest tercile at 31-weeks PMA were 7.6 times more likely to develop mild and severe ROP (95% CI 2.1-24.0, p value = 0.0006) and this risk increased to 12.3 times (95% CI: 2.6-59.0, p value = 0.0017) at 34-weeks PMA.

Conclusions: Low HbF levels at 31- and 34-weeks PMA are associated with significantly increased risk of developing ROP. The decrease in HbF precedes the development of ROP and may be important in its pathogenesis.
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http://dx.doi.org/10.1038/s41433-020-0938-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027597PMC
February 2021

Towards Bimanual Robot-Assisted Retinal Surgery: Tool-to-Sclera Force Evaluation.

Proc IEEE Sens 2018 Oct 27;2018. Epub 2018 Dec 27.

LCSR at the Johns Hopkins University, Baltimore, MD 21218 USA.

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 ( = 0.004). Moreover, the average forces under robot-assisted conditions with the present steady hand robot is notably higher than freehand conditions( = 0.01). The forces obtained from the dominant and not-dominant hand instruments indicate a weak correlation.
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http://dx.doi.org/10.1109/ICSENS.2018.8589810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677262PMC
October 2018

User Behavior Evaluation in Robot-Assisted Retinal Surgery.

ROMAN 2018 Aug 8;2018:174-179. Epub 2018 Nov 8.

LCSR at the Johns Hopkins University, Baltimore, MD 21218 USA

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.
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http://dx.doi.org/10.1109/ROMAN.2018.8525638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430218PMC
August 2018

Robot-assisted tremor control for performance enhancement of retinal microsurgeons.

Br J Ophthalmol 2019 08 20;103(8):1195-1200. Epub 2018 Dec 20.

Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

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.
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http://dx.doi.org/10.1136/bjophthalmol-2018-313318DOI Listing
August 2019

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

Int J Mol Sci 2018 Nov 21;19(11). Epub 2018 Nov 21.

Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

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.
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http://dx.doi.org/10.3390/ijms19113688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274767PMC
November 2018

Real-Time Sclera Force Feedback for Enabling Safe Robot-Assisted Vitreoretinal Surgery.

Annu Int Conf IEEE Eng Med Biol Soc 2018 Jul;2018:3650-3655

One of the major yet little recognized challenges in robotic vitreoretinal surgery is the matter of tool forces applied to the sclera. Tissue safety, coordinated tool use and interactions between tool tip and shaft forces are little studied. The introduction of robotic assist has further diminished the surgeon's ability to perceive scleral forces. Microsurgical tools capable of measuring such small forces integrated with robotmanipulators may therefore improve functionality and safety by providing sclera force feedback to the surgeon. In this paper, using a force-sensing tool, we have conducted robotassisted eye manipulation experiments to evaluate the utility of providing scleral force feedback. The work assesses 1) passive audio feedback and 2) active haptic feedback and evaluates the impact of these feedbacks on scleral forces in excess of aboundary. The results show that in presence of passive or active feedback, the duration of experiment increases, while the duration for which scleral forces exceed a safe threshold decreases.
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http://dx.doi.org/10.1109/EMBC.2018.8513255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6241282PMC
July 2018

Robot-assisted vitreoretinal surgery: current perspectives.

Robot Surg 2018 23;5:1-11. Epub 2018 Feb 23.

Department of Ophthalmology, Federal University of São Paulo, São Paulo, Brazil.

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.
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http://dx.doi.org/10.2147/RSRR.S122301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842029PMC
February 2018

CHOROIDAL NEOVASCULARIZATION ASSOCIATED WITH RETINAL PIGMENT EPITHELIAL TEAR IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

Retin Cases Brief Rep 2020 ;14(4):386-389

Department of Ophthalmology, Federal University of São Paulo, São Paulo, Brazil; and.

Purpose: To report a patient presenting a retinal pigment epithelial tear in which optical coherence tomography angiography enabled the visualization of subfoveal choroidal neovascularization (CNV) not evidenced by the fluorescein angiography. She was treated with 3 monthly intravitreous anti-VEGF injections and intraretinal fluid resolution occurred.

Methods: Observational case report.

Results: A 62-year-old Caucasian woman presented with decreased visual acuity in the right eye for 3 months. Fundus biomicroscopy revealed a yellowish macular lesion associated with intraretinal hemorrhage. Fluorescein angiography showed a large hyperfluorescent area consistent with window defect. Optical coherence tomography showed a retinal pigment epithelial tear with subretinal fluid. However, there was no clear evidence of CNV on fluorescein angiography or OCT. Optical coherence tomography angiography confirmed the presence of an active CNV by the visualization of the neovascular network in the region corresponding to the scrolled up retinal pigment epithelium.

Conclusion: This case report demonstrates that optical coherence tomography angiography can be useful to confirm the presence of CNV in cases where fluorescein angiography and OCT cannot establish the diagnosis. The reported case suggests the applicability of optical coherence tomography angiography in patients in whom retinal pigment epithelial tear is detected and associated CNV is suspected.
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http://dx.doi.org/10.1097/ICB.0000000000000721DOI Listing
July 2021

Optical coherence tomography angiography artifactual choroidal neovascularization in optic disc pit maculopathy.

Arq Bras Oftalmol 2017 Jul-Aug;80(4):257-259

Department of Ophthalmology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.

This case report describes a 19-year-old Caucasian man presented with decreased visual acuity in the right eye for 3 months. Dilated funds exam revealed optic disk pit associated with serous macular detachment. Optical coherence tomography identified communication between the optic disk pit and the macular serous detachment, and optical coherence tomography angiography displayed a subfoveal area suggestive of subfoveal choroidal neovascularization. However, there was no evidence of leakage in the fluorescein angiogram and no evidence of choroidal neovascularization in optical coherence tomography in the area corresponding to the suspicious subfoveal choroidal neovascularization. The patient underwent 23-gauge pars plana vitrectomy in the right eye. Six weeks after surgery, multimodal imaging was repeated and there was near-complete resorption of the subretinal fluid. Optical coherence tomography angiography signal superimposed on optical coherence tomography B-scan also demonstrated normal choriocapillaris signal throughout the macula. In conclusion, optical coherence tomography angiography may produce artifacts in optic disk pit maculopathy that simulate choroidal neovascularization.
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http://dx.doi.org/10.5935/0004-2749.20170062DOI Listing
December 2017

MACROANEURYSMS ASSOCIATED WITH CONGENITAL RETINAL MACROVESSELS.

Retin Cases Brief Rep 2020 ;14(1):61-65

Vitreous Retina Macular Consultants of New York, New York, New York.

Purpose: Congenital retinal macrovessels are large aberrant retinal blood vessels that cross the horizontal raphe and can traverse the central macula. Using multimodal imaging and optical coherence tomography angiography, we describe 2 cases of congenital retinal macrovessel associated with macroaneurysms.

Methods: Two patients presented for evaluation and were found to have congenital retinal macrovessels associated with macroaneurysms. Color photography, optical coherence tomography, fundus autofluorescence fluorescein angiography, and optical coherence tomography angiography were performed and used to establish the diagnosis and monitor resolution at follow-up visits.

Results: The first patient presented with central vision loss in the right eye and was noted to have a ruptured macroaneurysm and scattered microaneurysms along the course of a venous macrovessel. After 3 months of observation, the patient's vision improved. The second patient presented for evaluation of a cataract in her left eye and was incidentally found to have an arterial macrovessel in her right eye with an associated macroaneurysm. Both cases demonstrated an intricate capillary network in the central macula best visualized on optical coherence tomography angiography.

Conclusion: Macroaneurysms can occur on both arterial and venous macrovessels. After rupture of these lesions, hemorrhage and exudation can resolve with observation alone. Macrovessels can also present with microaneurysms. Optical coherence tomography angiography can effectively image the complex capillary network associated with these vascular anomalies.
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http://dx.doi.org/10.1097/ICB.0000000000000619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807243PMC
August 2020

Asymptomatic Progression of Ocular Behçet's Disease.

Ophthalmic Surg Lasers Imaging Retina 2017 01;48(1):18-35

Background And Objective: To emphasize the importance of auxiliary exams to detect progression of ocular Behçet's disease (BD) in asymptomatic patients.

Patients And Methods: This was a retrospective review of the clinical records of a consecutive series of patients with BD and asymptomatic visual deterioration, imaged on fundus photograph (FP), visual field (VF), fluorescein angiography (FA), and optical coherence tomography (OCT).

Results: Patients presented with no clinical findings or with mild inflammation on ophthalmic examination. However, during follow-up, VF examination indicated a progressive enlargement of previously visualized scotomas. On FA, the authors detected leakage and ischemia. On OCT, there was macular anatomical disruption, and the FP showed areas of atrophic retina.

Conclusion: In patients with ocular BD, the visual acuity deterioration may be asymptomatic and progressive. This should justify the importance of early and sequential ancillary exams in the management of BD patients to detect subclinical ocular involvement. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:18-25.].
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http://dx.doi.org/10.3928/23258160-20161219-03DOI Listing
January 2017

Herpes zoster ophthalmicus and varicella zoster virus vasculopathy.

Arq Bras Oftalmol 2016 Apr;79(2):126-9

Department of Ophthalmology and Visual Science, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.

Herpes zoster (HZ) corresponds to the reactivation of varicella zoster virus (VZV). Among adults, the ophthalmic division of the trigeminal nerve is one of the most common sites of involvement. Vasculopathy caused by HZ is associated with significant morbidity and mortality, affecting structures such as the brain, which can lead to stroke. In this review, we analyzed the epidemiological and clinical aspects of the vascular involvement of VZV, focusing on the peculiarities of its association with ocular HZ. A review of the available literature indicated that ocular involvement of HZ was a risk factor for vasculopathy after adjusting for age, sex, body mass index, smoking, indicators of metabolic syndrome, and vascular and heart diseases. Considering the severity of this complication, vascular disease mediated by VZV requires early diagnosis and aggressive treatment. Finally, the anti-HZ vaccine has been recommended as a prophylactic measure in the elderly, but it should be used with caution in immunocompromised individuals.
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http://dx.doi.org/10.5935/0004-2749.20160038DOI Listing
April 2016

Relationship between Daytime Sleepiness and Intrinsically Photosensitive Retinal Ganglion Cells in Glaucomatous Disease.

J Ophthalmol 2016 3;2016:5317371. Epub 2016 Feb 3.

Department of Ophthalmology, Federal University of São Paulo, Rua Botucatu, 821 Vila Clementino, 04023-062 São Paulo, SP, Brazil.

Patients with glaucoma showed to have higher daytime sleepiness measured by Epworth sleepiness scale. In addition, this symptom was associated with pupillary reflex and polysomnography parameters. These ipRGC functions might be impaired in patients with glaucoma, leading to worse quality of life.
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http://dx.doi.org/10.1155/2016/5317371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756205PMC
March 2016

Intrinsically photosensitive retinal ganglion cell activity is associated with decreased sleep quality in patients with glaucoma.

Ophthalmology 2015 Jun 7;122(6):1139-48. Epub 2015 Apr 7.

Ophthalmology Department, Federal University of São Paulo, São Paulo, Brazil.

Purpose: To use the pupillary light reflex and polysomnography to evaluate the function of intrinsically photosensitive retinal ganglion cells (ipRGCs) and to correlate this function with structural damage in glaucoma.

Design: Cross-sectional study.

Participants: A study was conducted on both eyes of 45 participants (32 patients with glaucoma and 13 healthy subjects).

Methods: For the pupillary reflex evaluation, patients were tested in the dark using a Ganzfeld system (RETIport; Roland Consult, Brandenburg, Germany); pupil diameter was measured with an eye tracker system. To preferentially stimulate ipRGCs, we used a 1-second 470-nm flash with a luminance of 250 cd/m(2). To stimulate different retinal photoreceptors, we used a 1-second 640-nm flash with a luminance of 250 cd/m(2). All of the subjects underwent polysomnography. Subjects underwent standard automated perimetry and optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec Inc, Dublin, CA).

Main Outcome Measures: Correlations between ipRGC activity, as measured by the pupillary light reflex, and polysomnography parameters, and correlations between retinal nerve fiber layer (RNFL) thickness and the pupillary light reflex and polysomnography parameters.

Results: The mean patient ages in the healthy and glaucoma groups were 56.8±7.8 years and 61.5±11.6 years, respectively (P = 0.174). Patients with glaucoma had significantly lower average total sleep time, sleep efficiency, and minimum oxyhemoglobin saturation compared with the healthy subjects (P  = 0.008, P = 0.002, and P = 0.028, respectively). Patients with glaucoma had significantly higher arousal durations after falling asleep and more periodic limb movements (P = 0.002 and P = 0.045, respectively). There was an inverse correlation between the rapid eye movement latency and the peak of the pupillary response to the blue flash (P = 0.004). The total arousals were inversely correlated with the sustained blue flash response (P = 0.029). The RNFL thickness was associated with the peak and sustained responses to the blue flash (P  <  0.001 for both comparisons); however, RNFL thickness was only associated with the mean oxygen desaturation index among the polysomnography parameters (P = 0.023).

Conclusions: This study demonstrated that decreased ipRGC function caused by glaucoma affected pupillary response and sleep quality.
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http://dx.doi.org/10.1016/j.ophtha.2015.02.030DOI Listing
June 2015

A positive association between intrinsically photosensitive retinal ganglion cells and retinal nerve fiber layer thinning in glaucoma.

Invest Ophthalmol Vis Sci 2014 Nov 18;55(12):7997-8005. Epub 2014 Nov 18.

Ophthalmology Department, Federal University of São Paulo, São Paulo, Brazil.

Purpose: To assess the integrity of intrinsically photosensitive retinal ganglion cells (ipRGCs) using the pupillary light reflex in glaucoma patients.

Methods: A cross-sectional study was conducted, including 76 eyes from 38 patients with primary open-angle glaucoma and 36 eyes from 18 control subjects. The patients were tested in the dark with light stimuli using the Ganzfeld system, and the pupil diameter was measured with the assistance of an eye tracker consisting of two infrared cameras fit to an eyeglass frame. To preferentially stimulate ipRGCs, we used a 1-second 470-nm flash with a luminance of 250 cd/m(2). To stimulate different retinal photoreceptors (cones and rods), we used a 1-second 630-nm flash with a luminance of 250 cd/m(2). Standard automated perimetry (SAP), matrix frequency-doubling technology (FDT), and high-definition optical coherence tomography (Cirrus HD-OCT) were also performed. The correlation between the ipRGC-mediated sustained response following the pupillary light reflex and the structural and functional changes in glaucoma patients was analyzed using generalized estimating equation.

Results: An association was observed between the average retinal nerve fiber layer (RNFL) thickness, as measured by Cirrus HD-OCT, and the sustained pupillary response to the blue flash (P = 0.024). The severity of glaucoma, based on the mean deviation of SAP (Hodapp-Anderson-Parrish system), was also associated with the sustained response to the blue flash (P = 0.006).

Conclusions: This study showed a correlation between the mean RNFL thickness and the pupillary light response. A decrease in the number of ipRGCs is potentially related to the reduced RNFL thickness.
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http://dx.doi.org/10.1167/iovs.14-15146DOI Listing
November 2014

Priapism is associated with sleep hypoxemia in sickle cell disease.

J Urol 2012 Oct 16;188(4):1245-51. Epub 2012 Aug 16.

Disciplina de Hematologia e Hemoterapia, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, São Paulo, Brazil.

Purpose: We assessed penile rigidity during sleep and the relationship of sleep abnormalities with priapism in adults with sickle cell disease.

Materials And Methods: This was a case-control study of 18 patients with sickle cell disease and a history of priapism during the previous year, and 16 controls with sickle cell disease. Participants underwent overnight polysomnography and RigiScan® Plus recording to detect penile rigidity oscillations.

Results: The priapism group (cases) showed a higher apnea-hypopnea index and oxyhemoglobin desaturation parameters than controls. A lower positive correlation between the apnea-hypopnea index and oxyhemoglobin desaturation time was observed in cases than in controls (Spearman coefficient ρ = 0.49, p = 0.05 vs ρ = 0.76, p <0.01), suggesting that desaturation events occurred independently of apnea. Two controls and 14 cases had a total sleep time that was greater than 10% with oxyhemoglobin saturation less than 90% but without CO(2) retention. Penile rigidity events were observed during rapid eye movement sleep and during stage 2 of nonrapid eye movement sleep, particularly in cases. The duration of penile rigidity events concomitant to respiratory events was higher in cases than in controls. Regression analysis revealed that the periodic limb movement and desaturation indexes were associated with priapism after adjusting for rapid eye movement sleep and lung involvement. Finally, oxyhemoglobin saturation less than 90% was associated with priapism after adjusting for lung involvement, hyperhemolysis and the apnea-hypopnea index.

Conclusions: Oxyhemoglobin desaturation during sleep was associated with priapism history. It may underlie the distribution pattern of penile rigidity events during sleep in these patients.
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http://dx.doi.org/10.1016/j.juro.2012.06.015DOI Listing
October 2012

Effects of sildenafil on autonomic nervous function during sleep in obstructive sleep apnea.

Clinics (Sao Paulo) 2010 Apr;65(4):393-400

Department of Psychobiology, Universidade Federal de São Paulo - São Paulo, Brazil.

Objective: To evaluate the effects of sildenafil on the autonomic nervous system in patients with severe obstructive sleep apnea.

Methods: Thirteen male patients with severe obstructive sleep apnea (mean age 43+/-10 years with a mean body mass index of 26.7+/-1.9 kg/m(2)) received a single 50-mg dose of sildenafil or a placebo at bedtime. All-night polysomnography and heart rate variability were recorded. Frequency domain analysis of heart rate variability was performed for the central five-minute sample of the longest uninterrupted interval of slow wave and rapid eye movement sleep, as well as for one-minute samples during apnea and during slow wave and rapid eye movement sleep after resumption of respiration.

Results: Compared to the placebo, sildenafil was associated with an increase in the normalized high-frequency (HF(nu)) components and a decrease in the low/high-frequency components of the heart rate variability ratio (LF/HF) in slow wave sleep (p<0.01 for both). Differences in heart rate variability parameters between one-minute post-apnea and apnea samples (Delta = difference between resumption of respiration and apnea) were assessed. A trend toward a decreasing magnitude of DeltaLF activity was observed during rapid eye movement sleep with sildenafil in comparison to placebo (p=0.046). Additionally, DeltaLF/HF in SWS and rapid eye movement sleep was correlated with mean desaturation (s(R =) -0.72 and -0.51, respectively, p= 0.01 for both), and DeltaHF(nu) in rapid eye movement sleep was correlated with mean desaturation (s(R=) 0.66, p= 0.02) and the desaturation index (s(R=) 0.58, p = 0.047).

Conclusions: The decrease in arousal response to apnea/hypopnea events along with the increase in HF(nu) components and decrease in LH/HF components of the heart rate variability ratio during slow wave sleep suggest that, in addition to worsening sleep apnea, sildenafil has potentially immediate cardiac effects in patients with severe obstructive sleep apnea.
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http://dx.doi.org/10.1590/S1807-59322010000400008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862674PMC
April 2010
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