Publications by authors named "Lejla Vajzovic"

65 Publications

Pediatric Vitreoretinal Surgery and Integrated Intraoperative Optical Coherence Tomography.

Dev Ophthalmol 2021 1;61:15-25. Epub 2021 Mar 1.

Retina Division, Duke Eye Center, Durham, North Carolina, USA,

Intraoperative portable handheld and microscope-integrated OCT enhance the pediatric vitreoretinal surgeon's diagnostic abilities during examination under anesthesia and surgery, particularly in children who are challenging to examine preoperatively due to young age or ocular trauma. Improved OCT-guided visualization of vitreoretinal anatomic relationships has the potential to improve surgical safety and efficiency. In retinopathy of prematurity and other pediatric retinal vascular conditions, intraoperative OCT can be critical for distinguishing between retinoschisis and retinal detachment and highlighting abnormalities of the vitreoretinal interface that may contribute to development of tractional retinal detachments. During retinal detachment repair, intraoperative OCT aids identification of subtle retinal breaks, residual subretinal fluid, retained perfluorocarbon, preretinal membranes, and residual hyaloid, among other findings. In macular surgery, intraoperative OCT has demonstrated value in confirming completion or lack thereof of epiretinal and internal limiting membrane peeling and differentiating between lamellar and full-thickness macular holes. OCT-guided subretinal bleb formation and genetic vector delivery are critical to ensuring accurate localization of subretinal gene delivery for inherited retinal degenerations. Research on development of OCT-compatible surgical instruments, real-time three-dimensional volumetric OCT imaging, and integration with intraoperative OCT angiography are anticipated to further increase the utility of intraoperative OCT in pediatric vitreoretinal surgical decision-making.
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http://dx.doi.org/10.1159/000511818DOI Listing
March 2021

Valsalva-Induced Retinal Hemorrhage as a Secondary Effect of COVID-19 Disease.

Asia Pac J Ophthalmol (Phila) 2021 Jan-Feb 01;10(1):125-126

Duke University Eye Center, Durham, NC, USA.

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http://dx.doi.org/10.1097/APO.0000000000000358DOI Listing
February 2021

Initial Presentation of Cutibacterium (Formerly Propionibacterium) acnes Endophthalmitis Twenty-One Years After Cataract Surgery.

Ophthalmic Surg Lasers Imaging Retina 2021 01;52(1):44-46

The authors report a case of an 81-year-old female who presented with sudden onset of light perception vision and intraocular inflammation. After several months of continuing symptoms despite antibiotics, an aqueous tap culture grew Cutibacterium acnes. The patient had cataract surgery 21 years prior, and had no intervening trauma, intraocular procedure, or endogenous source. The presumed diagnosis was C. acnes endophthalmitis with significantly delayed onset. Capsulectomy and intraocular lens removal resolved the patient's symptoms. In rare cases, C. acnes endophthalmitis may present as recurrent inflammation despite an extremely remote history of cataract surgery, mimicking a virulent, acute-onset endophthalmitis despite antibiotic administration. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:44-46.].
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http://dx.doi.org/10.3928/23258160-20201223-08DOI Listing
January 2021

Optical coherence tomography imaging of the pediatric retina.

J AAPOS 2020 10 14;24(5):261-267. Epub 2020 Oct 14.

Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina. Electronic address:

Optical coherence tomography is an increasingly important part of the retinal specialist's and general ophthalmologist's toolkit for diagnosing and managing retinal disease. This review summarizes the unique considerations and available imaging systems with which pediatric ophthalmologists should be familiar when attempting optical coherence tomography in children. Normal developmental changes in foveal and extrafoveal structure and the need for an established pediatric normative database of retinal thicknesses are reviewed. Finally, applications of optical coherence tomography imaging to selected representative pediatric retinal diseases are introduced as examples of how optical coherence tomography in children is furthering the diagnosis and management of vision-threatening retinal diseases.
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http://dx.doi.org/10.1016/j.jaapos.2020.05.019DOI Listing
October 2020

Clinicopathologic correlation of aniridia: Optical coherence tomography angiography and histopathologic observations.

Am J Ophthalmol Case Rep 2020 Dec 11;20:100919. Epub 2020 Sep 11.

Department of Ophthalmology, Duke University, Durham, NC, USA.

Purpose: To describe optical coherence tomography angiography (OCTA) findings in a patient with aniridia and correlate with representative histopathology.

Observations: OCTA images of the macula of a pediatric aniridic patient, who has nystagmus and impaired vision bilaterally, demonstrate a complete absence of the foveal avascular zone (FAZ) in both the superficial and deep vascular complexes (SVC and DVC). In addition, larger superficial blood vessels were found to be abnormally diving from the SVC into the DVC. Similarly, immunofluorescence with confocal microscopy imaging of a retinal histopathology specimen from a 2 month old aniridic patient demonstrated larger vessels diving in the same manner.

Conclusions And Importance: This study highlights the clinical, imaging and histopathologic findings of aniridia. Supine OCTA imaging, performed during examination under anesthesia, allowed for visualization of retinal microvasculature in eyes with nystagmus. The histopathology images helped validate OCTA findings that, with further investigation, may lead to new information about the development of abnormal retinal microvasculature.
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http://dx.doi.org/10.1016/j.ajoc.2020.100919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522690PMC
December 2020

Morphological characteristics of early- versus late-onset macular edema in preterm infants.

J AAPOS 2020 10 15;24(5):303-306. Epub 2020 Sep 15.

Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina; Department of Biomedical Engineering, Duke University School of Medicine, Durham, North Carolina. Electronic address:

Macular images of infants with early-onset edema (occurring at or before 33 weeks' postmenstrual age [PMA]) and infants with late-onset edema (at or after 36 weeks' PMA) were compared. At first appearance, early-onset edema has a more severe morphology, with foveal bulging and elongated cystoid spaces than late-onset edema, which presents as small cystoid spaces outside the foveal center. Morphological variations may be an indicator of the underlying cause of edema in preterm infants. The presence of mostly parafoveal small cystoid spaces in the late-onset edema group may be suggestive of an association with neurological injury.
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http://dx.doi.org/10.1016/j.jaapos.2020.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006576PMC
October 2020

Macular OCT Characteristics at 36 Weeks' Postmenstrual Age in Infants Examined for Retinopathy of Prematurity.

Ophthalmol Retina 2020 Sep 11. Epub 2020 Sep 11.

Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina; Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, North Carolina. Electronic address:

Purpose: To report our ability to capture,-grade reliably, and analyze bedside macular OCT images from preterm infants and relate OCT findings to biological factors and retinopathy of prematurity (ROP) status at a single time window in the Study of Eye Imaging in Preterm Infants (BabySTEPS).

Design: Prospective, observational study.

Participants: Preterm infants eligible for ROP screening with parental consent for research and a 36 ± 1 weeks' postmenstrual age (PMA) visit.

Methods: We imaged both eyes of preterm infants with an investigational noncontact, handheld swept-source (SS) OCT at the time of clinical ROP examinations. Macular OCT features and layer thicknesses for untreated eyes of infants at 36 ± 1 weeks' PMA were compared with demographic data and clinical ROP examination performed by experts. Statistical analyses accounted for the use of both eyes of infants.

Main Outcome Measures: Macular OCT features and layer thicknesses, gender, race or ethnicity, gestational age, birth weight, ROP stage, and plus disease.

Results: We captured macular OCT from 169 eyes (1 eye excluded because of prior ROP treatment) at 36 ± 1 weeks' PMA. The quality of OCT volumes was excellent in 33 eyes (19%), acceptable in 112 eyes (67%), poor in 24 eyes (14%), and unusable in 0 eyes (0%). Macular edema was present in 60% of eyes and was bilateral in 82% of infants with edema. At the fovea, retinal and inner nuclear layer thickness increased with edema severity: 183 ± 36 μm and 51 ± 27 μm in mild (16% of eyes), 308 ± 57 μm and 163 ± 53 μm in moderate (25%), and 460 ± 76 μm and 280 ± 83 μm in severe edema (12%), respectively. With an increase in ROP stage from 0 to 2, the mean ± standard deviation retinal thickness at the fovea increased from 227± 124 μm to 297 ± 99 μm (P < 0.001). The choroid was thinner, 155 ± 72 μm, with preplus or plus disease versus without, 236 ± 79 μm (P = 0.04), whereas retinal thickness did not vary.

Conclusions: We demonstrated the reliability of methods and the prevalence of OCT findings in preterm infants enrolled in BabySTEPS at a single time point of 36 ± 1 weeks' PMA. Variations in layer thicknesses in infants at this time point may reflect abnormalities resulting from delay in foveal development that may be impacted by macular edema, ROP, or both.
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http://dx.doi.org/10.1016/j.oret.2020.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947027PMC
September 2020

Lightweight Learning-Based Automatic Segmentation of Subretinal Blebs on Microscope-Integrated Optical Coherence Tomography Images.

Am J Ophthalmol 2021 01 21;221:154-168. Epub 2020 Jul 21.

Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA; Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, USA. Electronic address:

Purpose: Subretinal injections of therapeutics are commonly used to treat ocular diseases. Accurate dosing of therapeutics at target locations is crucial but difficult to achieve using subretinal injections due to leakage, and there is no method available to measure the volume of therapeutics successfully administered to the subretinal location during surgery. Here, we introduce the first automatic method for quantifying the volume of subretinal blebs, using porcine eyes injected with Ringer's lactate solution as samples.

Design: Ex vivo animal study.

Methods: Microscope-integrated optical coherence tomography was used to obtain 3D visualization of subretinal blebs in porcine eyes at Duke Eye Center. Two different injection phases were imaged and analyzed in 15 eyes (30 volumes), selected from a total of 37 eyes. The inclusion/exclusion criteria were set independently from the algorithm-development and testing team. A novel lightweight, deep learning-based algorithm was designed to segment subretinal bleb boundaries. A cross-validation method was used to avoid selection bias. An ensemble-classifier strategy was applied to generate final results for the test dataset.

Results: The algorithm performs notably better than 4 other state-of-the-art deep learning-based segmentation methods, achieving an F1 score of 93.86 ± 1.17% and 96.90 ± 0.59% on the independent test data for entry and full blebs, respectively.

Conclusion: The proposed algorithm accurately segmented the volumetric boundaries of Ringer's lactate solution delivered into the subretinal space of porcine eyes with robust performance and real-time speed. This is the first step for future applications in computer-guided delivery of therapeutics into the subretinal space in human subjects.
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http://dx.doi.org/10.1016/j.ajo.2020.07.020DOI Listing
January 2021

Retinal Vasculitis and Intraocular Inflammation after Intravitreal Injection of Brolucizumab.

Ophthalmology 2020 10 25;127(10):1345-1359. Epub 2020 Apr 25.

Bascom Palmer Eye Institute, University of Miami Leonard M. Miller School of Medicine, Miami, Florida.

Purpose: To evaluate features and outcomes of eyes with retinal vasculitis and intraocular inflammation (IOI) after intravitreal injection (IVI) of brolucizumab 6 mg/0.05 ml for treatment of neovascular age-related macular degeneration.

Design: Retrospective case series.

Participants: Fifteen eyes from 12 patients identified from 10 United States centers.

Methods: Review of patient demographics, ophthalmologic examination results, and retinal imaging findings.

Main Outcome Measures: Baseline and follow-up visual acuity (VA), prior anti-vascular endothelial growth factor (VEGF) injections, clinical presentation, retinal findings, fluorescein angiography results, and treatment strategies.

Results: The number of previous anti-VEGF IVIs ranged between 2 and 80 in the affected eye before switching to brolucizumab. Retinal vasculitis and IOI were diagnosed at a mean of 30 days after brolucizumab IVI. Mean VA before brolucizumab IVI was 0.426 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/53) and VA at diagnosis of retinal vasculitis was 0.981 logMAR (Snellen equivalent, 20/191; range, 20/25-20/1600; P = 0.008). All affected eyes showed IOI with variable combinations of focal or elongated segmental sheathing and discontinuity of small and large retinal arteries, sclerotic arteries, regions of vascular nonperfusion, cotton-wool spots, Kyrieleis plaques, irregular venous caliber with dilated and sclerotic segments, perivenular hemorrhages, and foci of phlebitis. Fluorescein angiography revealed delayed retinal arterial filling, retinal vascular nonperfusion, and variable dye leakage from affected vessels and the optic nerve. Systemic evaluation for embolic causes was unrevealing in 2 patients, and 3 patients showed negative laboratory assessment for uveitis. Treatment consisted of various combinations of corticosteroids (systemic, intravitreal, and topical), and 2 eyes underwent vitrectomy without improvement in vision. After a mean follow-up of 25 days, mean VA was 0.833 logMAR (Snellen equivalent, 20/136), which was reduced compared with baseline (P = 0.033).

Conclusions: Retinal vasculitis and IOI after brolucizumab IVI are characterized by variable occlusion of large or small retinal arteries, or both, and perivenular abnormalities. It may span from peripheral vasculitis to occlusion of large retinal arteries around the optic nerve or macula with severe vision loss. A high index of suspicion is required because vitreous cells may obscure visualization of retinal details.
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http://dx.doi.org/10.1016/j.ophtha.2020.04.017DOI Listing
October 2020

INTRAOPERATIVE OPTICAL COHERENCE TOMOGRAPHY AND ENDOSCOPY-GUIDED EXPLANTATION OF ARGUS II DEVICE.

Retin Cases Brief Rep 2020 Mar 17. Epub 2020 Mar 17.

Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina.

Purpose: To describe a surgical approach using intraoperative optical coherence tomography and endoscopy for successful Argus II retinal prosthesis system removal.

Methods: Retrospective review of a patient undergoing Argus II explantation 8 months after initial implantation.

Results: Successful explantation of the Argus II device was performed in this patient.

Conclusion: Explantation of the Argus II device can be a difficult surgery, and intraoperative optical coherence tomography and endoscopy can be used to help avoid potential complications.
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http://dx.doi.org/10.1097/ICB.0000000000000994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494642PMC
March 2020

Recent developments in pediatric retina.

Curr Opin Ophthalmol 2020 May;31(3):155-160

Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA.

Purpose Of Review: Pediatric retina is an exciting, but also challenging field, where patient age and cooperation can limit ease of diagnosis of a broad range of congenital and acquired diseases, inherited retinal degenerations are mostly untreatable and surgical outcomes can be quite different from those for adults. This review aims to highlight some recent advances and trends that are improving our ability to care for children with retinal conditions.

Recent Findings: Studies have demonstrated the feasibility of multimodal imaging even in nonsedated infants, with portable optical coherence tomography (OCT) and OCT angiography in particular offering structural insights into diverse pediatric retinal conditions. Encouraging long-term outcomes of subretinal voretigene neparvovec-rzyl injection for RPE65 mutation-associated Leber congenital amaurosis have inspired research on the optimization of subretinal gene delivery and gene therapy for other inherited retinal degenerations. In retinopathy of prematurity, machine learning and smartphone-based imaging can facilitate screening, and studies have highlighted favorable outcomes from intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. A nomogram for pediatric pars plana sclerotomy site placement may improve safety in complex surgeries.

Summary: Multimodal imaging, gene therapy, machine learning and surgical innovation have been and will continue to be important to advances in pediatric retina.
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http://dx.doi.org/10.1097/ICU.0000000000000650DOI Listing
May 2020

ADVERSE EVENTS OF THE ARGUS II RETINAL PROSTHESIS: Incidence, Causes, and Best Practices for Managing and Preventing Conjunctival Erosion.

Retina 2020 Feb;40(2):303-311

Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Purpose: To analyze and provide an overview of the incidence, management, and prevention of conjunctival erosion in Argus II clinical trial subjects and postapproval patients.

Methods: This retrospective analysis followed the results of 274 patients treated with the Argus II Retinal Prosthesis System between June 2007 and November 2017, including 30 subjects from the US and European clinical trials, and 244 patients in the postapproval phase. Results were gathered for incidence of a serious adverse event, incidence of conjunctival erosion, occurrence sites, rates of erosion, and erosion timing.

Results: Overall, 60% of subjects in the clinical trial subjects versus 83% of patients in the postapproval phase did not experience device- or surgery-related serious adverse events. In the postapproval phase, conjunctival erosion had an incidence rate of 6.2% over 5 years and 11 months. In 55% of conjunctival erosion cases, erosion occurred in the inferotemporal quadrant, 25% in the superotemporal quadrant, and 20% in both. Sixty percent of the erosion events occurred in the first 15 months after implantation, and 85% within the first 2.5 years.

Conclusion: Reducing occurrence of conjunctival erosion in patients with the Argus II Retinal Prosthesis requires identification and minimization of risk factors before and during implantation. Implementing inverted sutures at the implant tabs, use of graft material at these locations as well as Mersilene rather than nylon sutures, and accurate Tenon's and conjunctiva closure are recommended for consideration in all patients.
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http://dx.doi.org/10.1097/IAE.0000000000002394DOI Listing
February 2020

Microvascular Features of Treated Retinoblastoma Tumors in Children Assessed Using OCTA.

Ophthalmic Surg Lasers Imaging Retina 2019 12;51(1):43-49

Background And Objective: To describe the microvascular features of treated, clinically regressed, or reactivated retinoblastoma lesions using an investigational portable optical coherence tomography angiography (OCTA) system.

Patients And Methods: Single-center, prospective, cross-sectional, consecutive case-series of children with previously treated retinoblastoma who underwent portable OCTA of posterior retinoblastoma lesions.

Results: Eight tumors from seven eyes of five children with retinoblastoma were included. Tumors with types 1 (calcified remnant, n = 3), 2 (non-calcified remnant, n = 1), and 3 (both calcified and noncalcified remnants, n = 1) regression revealed persistent intrinsic superficial vasculature on OCTA (five of five lesions; 100%). Lesions with type 4 regression (atrophic scar, n = 2) had complete vascular flow voids in the involved retina and underlying choriocapillaris. A reactivated tumor (n = 1) showed a distinct area of vascularity with prominent feeder/draining vessels.

Conclusions: OCTA revealed that significant vascularity exists in inactive retinoblastoma lesions. Dilated feeder vessels may suggest continued disease activity. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:43-49.].
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http://dx.doi.org/10.3928/23258160-20191211-06DOI Listing
December 2019

Differentiating Retinal Detachment and Retinoschisis Using Handheld Optical Coherence Tomography in Stage 4 Retinopathy of Prematurity.

JAMA Ophthalmol 2020 Jan;138(1):81-85

Department of Ophthalmology, Duke University, Durham, North Carolina.

Importance: Progression of retinopathy of prematurity (ROP) to stage 4 may require surgical intervention. The partial retinal detachment of stage 4 ROP may involve the fovea (stage 4B ROP) or may not (stage 4A ROP). This determination has heretofore been based on indirect ophthalmoscopy and documented with color fundus photography.

Objective: To investigate optical coherence tomography (OCT) features of eyes with stage 4 ROP and compare them with indirect ophthalmoscopy findings and grading of photographs.

Design, Setting, And Participants: In this study, research and clinical medical records of 15 infants with clinically diagnosed stage 4 ROP were retrospectively reviewed. Infants were treated at an academic center from May 2011 to January 2018.

Main Outcomes And Measures: Review of OCT images for the presence and foveal involvement of retinoschisis, retinal detachment, and/or vitreomacular traction masked to indirect ophthalmoscopy findings.

Results: Of the 15 included infants, 9 (60%) were male, the mean (SD) gestational age at birth was 23.9 (1.1) weeks, and the mean (SD) postmenstrual age at surgery was 42.4 (4.9) weeks. A total of 21 eyes were analyzed, of which 19 had adequate OCT imaging. Optical coherence tomography imaging extended to the retinal midperiphery but did not cover the entire region of possible detachment in each eye. Among these eyes, 7 eyes had peripheral retinoschisis without retinal detachment or foveal involvement, 5 eyes had peripheral retinoschisis and retinal detachment without foveal involvement, 7 eyes had either retinoschisis or retinal detachment involving the fovea, and 2 eyes had poor OCT signal owing to high retinal detachment.

Conclusions And Relevance: Handheld OCT imaging is useful in clinical evaluation of stage 4 ROP to determine foveal involvement and differentiate retinal detachment and retinoschisis. Many infants diagnosed as having stage 4A ROP had retinoschisis without OCT evidence of retinal detachment. This group of infants may represent a substage of stage 4A ROP, ie, stage 4A-schisis by OCT. These findings suggest handheld OCT imaging may be useful in the clinical evaluation of stage 4 ROP. Further investigations are needed to determine if this subgroup portends a different prognosis and if this observation should alter future clinical practice.
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http://dx.doi.org/10.1001/jamaophthalmol.2019.4796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902125PMC
January 2020

HANDHELD SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS OF X-LINKED RETINOSCHISIS IN EARLY CHILDHOOD.

Retina 2020 Oct;40(10):1996-2003

Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina; and.

Background/purpose: Using handheld spectral domain optical coherence tomography (SDOCT) imaging to investigate in vivo microanatomic retinal changes and their progression over time in young children with juvenile X-linked retinoschisis (XLRS).

Methods: This retrospective analysis was of handheld SD OCT images obtained under a prospective research protocol in children who had established XLRS diagnosis based on genetic testing or clinical history. Three OCT graders performed standardized qualitative and quantitative assessment of retinal volume scans, which were divided into foveal, parafoveal, and extrafoveal regions. Visual acuity data were obtained when possible.

Results: Spectral domain OCT images were available of both eyes in 8 pediatric patients with ages 7 months to 10 years. The schisis cavities involved inner nuclear layer in over 90% (15/16) of eyes in all 3 regions. Retinal nerve fiber and ganglion cell layer involvement was present only in the extrafoveal region in 63% (10/16) eyes and outer nuclear and plexiform layer in few others. In 7 children followed over 2 months to 15 months, the location of schisis remained consistent. Central foveal thickness decreased from the baseline to final available visit in 4/6 eyes. Ellipsoid zone disruption seemed to accompany lower visual acuity in 1/4 eyes.

Conclusion: Early in life, the SD OCT findings in XLRS demonstrate differences in schisis location in fovea-parafoveal versus extrafoveal region, possible association between poor visual acuity and degree of ellipsoid zone disruption and decrease in central foveal thickness over time in this group. Furthermore, they illustrates that the pattern of XLRS in adults is already present in very young children, and unlike in older children and adults, those presenting with earlier disease may have a more aggressive course. Further studies in this early age group may provide more insights into treatment and prevention of progressive visual impairment in children with XLRS.
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http://dx.doi.org/10.1097/IAE.0000000000002688DOI Listing
October 2020

Appearance of pediatric choroidal neovascular membranes on optical coherence tomography angiography.

Graefes Arch Clin Exp Ophthalmol 2020 Jan 22;258(1):89-98. Epub 2019 Nov 22.

Department of Ophthalmology, Duke University Eye Center, Duke University School of Medicine, 2351 Erwin Road, Durham, NC, 27710, USA.

Purpose: Compared with fluorescein angiography (FA), the gold standard for diagnosing choroidal neovascularization (CNV) activity, optical coherence tomography angiography (OCTA) is non-invasive without risks associated with fluorescein dye use, and may be especially advantageous in the diagnosis and monitoring of children with CNV.

Methods: Eight eyes from eight patients aged 12 months to 18 years were imaged with the investigational Spectralis OCTA (version 6.9, Heidelberg Engineering, Heidelberg, Germany) and the RTVue XR Avanti (Optovue Inc., Fremont, CA, USA). Two patients were imaged during examination under anesthesia while six patients were imaged in the clinic. Demographic information, ocular characteristics, treatment history, and imaging studies (color photos, fluorescein angiography, OCT) were collected and reviewed.

Results: Three eyes had active CNV while five had quiescent CNV at the time of imaging. CNV was idiopathic or secondary to trauma, retinal vascular dysgenesis versus retinopathy of prematurity, pigmentary retinopathy, Best vitelliform macular dystrophy, panuveitis, morning glory disc anomaly, and optic disc drusen. OCTA of two active CNV demonstrated presence of a main trunk with multiple fine capillaries, vessel loops, and anastomoses. OCTA was repeated after treatment for two CNV and demonstrated a decrease in size with loss of fine capillaries, vessel loops, and anastomoses. For the third active CNV, OCTA verified flow in the CNV complex despite the uncertainty of FA hyperfluorescence in the setting of grossly abnormal retinal vasculature. The five quiescent CNV all lacked fine capillaries, vessel loops, and anastomoses on OCTA.

Conclusion: OCTA demonstrates morphological differences between active and quiescent pediatric CNV.
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http://dx.doi.org/10.1007/s00417-019-04535-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105393PMC
January 2020

Ophthalmic and Central Retinal Artery Occlusion Following Triamcinolone Injection of the Lacrimal Gland.

JAMA Ophthalmol 2019 Dec;137(12):1460-1461

Duke University Eye Center, Durham, North Carolina.

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http://dx.doi.org/10.1001/jamaophthalmol.2019.3998DOI Listing
December 2019

Assessment of Macular Microvasculature in Healthy Eyes of Infants and Children Using OCT Angiography.

Ophthalmology 2019 12 15;126(12):1703-1711. Epub 2019 Jul 15.

Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina. Electronic address:

Purpose: To assess macular vasculature in healthy infants and children using OCT angiography (OCTA).

Design: Prospective cross-sectional study.

Participants: One hundred thirty-five normal maculae of 89 healthy infants and children (mean age, 8.5±5.3 years; range, 9 weeks-17 years) treated at the Duke University Eye Center.

Methods: We imaged 135 maculae of 89 pediatric patients using the standard Spectralis tabletop and investigational Spectralis with Flex module devices, both equipped with investigational OCTA software (Heidelberg Engineering, Heidelberg, Germany). OCT angiography images of the superficial vascular complex (SVC) and deep vascular complex (DVC) were analyzed for foveal avascular zone (FAZ) area and superficial and deep vessel density. We assessed effects of age, gender, race, axial length (AL), and central subfield thickness on FAZ and vessel density. Patients with both eyes imaged were assessed for agreement between the FAZ and vessel densities of the left and right eyes.

Main Outcome Measures: The FAZ area, as well as vessel area density (VAD) and vessel length density (VLD) in the SVC and DVC.

Results: The FAZ varied significantly with race; white patients showed a significantly smaller FAZ than black patients (mean difference, 0.11 mm; P = 0.004). The FAZ did not vary with age, gender, or AL (P > 0.05). In the SVC, VAD and VLD varied significantly with age (P < 0.001) and AL (R = 0.46; P < 0.001) but not gender (P > 0.05). The SVC VLD was significantly different between races and ethnicities (P = 0.037), but VAD was not (P < 0.05). In the DVC, VAD and VLD also varied significantly with age (P < 0.001) and AL (R = 0.46; P < 0.001) but not gender or race (P > 0.05). There was excellent agreement between the right and left eyes for FAZ (intraclass correlation [ICC], 0.97), SVC VLD (ICC, 1.00), and DVC VLD (ICC, 1.00).

Conclusions: Quantitative studies of pediatric perifoveal vasculature should consider age, race, and AL. In eyes with unilateral disease, the perifoveal vasculature in the unaffected eye may be used as a control comparison because there is excellent agreement between eyes.
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http://dx.doi.org/10.1016/j.ophtha.2019.06.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875602PMC
December 2019

Analysis of Melanin Structure and Biochemical Composition in Conjunctival Melanocytic Lesions Using Pump-Probe Microscopy.

Transl Vis Sci Technol 2019 May 4;8(3):33. Epub 2019 Jun 4.

Department of Chemistry, Duke University, Durham, NC, USA.

Purpose: We analyze melanin structure and biochemical composition in conjunctival melanocytic lesions using pump-probe microscopy to assess the potential for this method to assist in melanoma diagnosis.

Methods: Pump-probe microscopy interrogates transient excited-state photodynamic properties of absorbing molecules, which yields highly specific molecular information with subcellular spatial resolution. This method is applied to analyze melanin in 39 unstained, thin biopsy specimens of melanocytic conjunctival lesions. Quantitative features of the biochemical composition and structure of melanin in histopathologic specimens are assessed using a geometric representation of principal component analysis (PCA) and principles of mathematical morphology. Diagnostic power is determined using a feature selection algorithm combined with cross validation.

Results: Conjunctival melanomas show higher biochemical heterogeneity and different overall biochemical composition than primary acquired melanosis of the conjunctiva (PAM) without severe atypia. The molecular signatures of PAMs with severe atypia more closely resemble melanomas than other types of PAMs. Pigment organization in the tissue becomes more disorganized as diagnosis of the lesions worsen, but nevi are more inconsistent biochemically and structurally than other lesions. Relatively high sensitivity (SE) and specificity (SP) is achieved for differentiating between various melanocytic lesions, particularly PAMs without severe atypia and melanomas (SE = 89%; SP = 87%).

Conclusions: Pump-probe microscopy is a powerful tool that can identify quantitative, phenotypic differences between various types of conjunctival melanocytic lesions.

Translational Relevance: This study further validates the use of pump-probe microscopy as a potential diagnostic aid for histopathologic evaluation of conjunctival melanocytic lesions.
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http://dx.doi.org/10.1167/tvst.8.3.33DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549561PMC
May 2019

Ergonomic handheld OCT angiography probe optimized for pediatric and supine imaging.

Biomed Opt Express 2019 May 29;10(5):2623-2638. Epub 2019 Apr 29.

Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.

OCT angiography is a functional extension of OCT that allows for non-invasive imaging of retinal microvasculature. However, most current OCT angiography systems are tabletop systems that are typically used for imaging compliant, seated subjects. These systems cannot be readily applied for imaging important patient populations such as bedridden patients, patients undergoing surgery in the operating room, young children in the clinic, and infants in the intensive care nursery. In this manuscript, we describe the design and development of a non-contact, handheld probe optimized for OCT angiography that features a novel diverging light on the scanner optical design that provides improved optical performance over traditional OCT scanner designs. Unlike most handheld OCT probes, which are designed to be held by the side of the case or by a handle, the new probe was optimized for ergonomics of supine imaging where imagers prefer to hold the probe by the lens tube. The probe's design also includes an adjustable brace that gives the operator a point of contact closer to the center of mass of the probe, reducing the moment of inertia around the operator's fingers, facilitating stabilization, and reducing operator fatigue. The probe supports high-speed imaging using a 200 kHz swept source OCT engine, has a motorized stage that provides + 10 to -10 D refractive error correction and weighs 700g. We present initial handheld OCT angiography images from healthy adult volunteers, young children during exams under anesthesia, and non-sedated infants in the intensive care nursery. To the best of our knowledge, this represents the first reported use of handheld OCT angiography in non-sedated infants, and the first handheld OCT angiography images which show the clear delineation of key features of the retinal capillary complex including the foveal avascular zone, peripapillary vasculature, the superficial vascular complex, and the deep vascular complex.
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http://dx.doi.org/10.1364/BOE.10.002623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524583PMC
May 2019

Macular Microvascular Findings in Familial Exudative Vitreoretinopathy on Optical Coherence Tomography Angiography.

Ophthalmic Surg Lasers Imaging Retina 2019 05;50(5):322-329

Background And Objective: To describe depth-resolved macular microvasculature abnormalities in patients with familial exudative vitreoretinopathy (FEVR) using optical coherence tomography angiography (OCTA).

Patients And Methods: Twenty-two eyes (11 eyes of six patients with FEVR and 11 control eyes) were imaged with OCTA. Graders qualitatively analyzed the OCTA images of the superficial and deep vascular complexes for abnormal vascular features and compared to fluorescein angiography (FA).

Results: Seven of 11 eyes with FEVR displayed abnormal macular vascular findings. Abnormalities in the superficial vascular complex included dilation, disorganization, straightening, heterogeneous vessel density, and curls/loops. In the deep vascular complex, abnormalities included areas of decreased density, disorganization, curls/loops, and "end bulbs." Except for dragging and straightening of the vessels, none of these macular features were visible on FA.

Conclusion: OCTA revealed marked macular abnormalities in eyes with FEVR that have not been previously observed with FA alone, suggesting this is more than a disease of the retinal periphery and involves macular and deep retinal vasculature abnormalities. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:322-329.].
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http://dx.doi.org/10.3928/23258160-20190503-11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980300PMC
May 2019

Longitudinal Study of Visual Function in Dry Age-Related Macular Degeneration at 12 Months.

Ophthalmol Retina 2019 08 21;3(8):637-648. Epub 2019 Mar 21.

Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina. Electronic address:

Purpose: To report the 1-year progression of visual impairment on psychophysical tests of visual function in patients with early and intermediate age-related macular degeneration (AMD).

Design: Prospective, observational study.

Participants: Patients with early and intermediate AMD were enrolled from the existing population at the Duke Eye Center, and healthy age-matched control participants were recruited from family members or friends of the AMD patients and from the Duke Optometry and Comprehensive Eye Clinics.

Methods: Patients and control participants recruited during the baseline study were assessed at both 6 and 12 months after the initial study visit. Measurements of visual function included best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), low-luminance deficit (LLD), microperimetry percent-reduced threshold (PRT), microperimetry average threshold (AT), and cone contrast tests (CCTs).

Main Outcome Measures: Changes in BCVA, LLVA, LLD, microperimetry PRT, microperimetry AT, and CCT results from baseline to 6 months and to 12 months were assessed.

Results: Eighty-five patients completed the 12-month examination (19 control participants, 27 early AMD patients, and 39 intermediate AMD patients). Longitudinal analysis detected significant changes from baseline within each group in microperimetry PRT and AT and in the intermediate AMD group only for BCVA and CCT results (P < 0.05).

Conclusions: Microperimetry and CCT are able to detect functional changes resulting from progression of dry AMD within a period as short as 12 months. These functional markers may be useful end points in future clinical trials that assess the effect of potential treatments for AMD.
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http://dx.doi.org/10.1016/j.oret.2019.03.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684849PMC
August 2019

Four-Dimensional Microscope-Integrated OCT Use in Argus II Placement.

Ophthalmol Retina 2018 05 21;2(5):510-511. Epub 2017 Dec 21.

Department of Ophthalmology, Duke University, Durham, North Carolina. Electronic address:

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http://dx.doi.org/10.1016/j.oret.2017.10.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7257262PMC
May 2018

Synergistic Visual Gains Attained using Argus II Retinal Prosthesis with OrCam MyEye.

Ophthalmol Retina 2018 04 12;2(4):382-384. Epub 2017 Oct 12.

Department of Ophthalmology, Duke University Medical Center, Durham, NC. Electronic address:

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http://dx.doi.org/10.1016/j.oret.2017.08.008DOI Listing
April 2018

Vascular Findings in a Small Retinoblastoma Tumor Using OCT Angiography.

Ophthalmol Retina 2019 02 29;3(2):194-195. Epub 2018 Sep 29.

Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina. Electronic address:

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http://dx.doi.org/10.1016/j.oret.2018.09.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056864PMC
February 2019

Imaging Infant Retinal Vasculature with OCT Angiography.

Ophthalmol Retina 2019 01 26;3(1):95-96. Epub 2018 Jul 26.

Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina. Electronic address:

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http://dx.doi.org/10.1016/j.oret.2018.06.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6816267PMC
January 2019

Hyperreflective Vitreous Opacities on Optical Coherence Tomography in a Patient With Bilateral Retinoblastoma.

Ophthalmic Surg Lasers Imaging Retina 2019 01;50(1):50-52

An investigational, portable spectral-domain optical coherence tomography (SD-OCT) unit revealed small hyperreflective opacities in both eyes of a patient with bilateral retinoblastoma. There was no evidence of vitreous seeding on ophthalmoscopy of either eye. Although the opacities may initially raise concern for potential vitreous seeding, this report suggests alternate potential etiologies for such opacities, which were also seen on imaging of a cohort of normal eyes in pediatric patients. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:50-52.].
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http://dx.doi.org/10.3928/23258160-20181212-08DOI Listing
January 2019

Comparison of Optical Coherence Tomography With Fundus Photographs, Fluorescein Angiography, and Histopathologic Analysis in Assessing Coats Disease.

JAMA Ophthalmol 2019 02;137(2):176-183

Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina.

Importance: Coats disease is a rare pediatric vitreoretinopathy that can cause devastating visual and anatomic outcomes.

Objective: To compare optical coherence tomography (OCT) with fundus photographs, fluorescein angiography (FA), and histopathologic findings in Coats disease.

Design, Setting, And Participants: This retrospective cohort study was conducted in a single tertiary institution (Duke Eye Center) and identified 28 children with Coats disease through a review of medical records from December 2002 to January 2018. Four eyes were obtained from a biorepository for histopathologic analysis.

Main Outcomes And Measures: Macular OCT, fundus photographs, and FA results were reviewed and compared for morphological changes. These were compared with retinal histopathological findings.

Results: The mean (SD) age was 9.5 (5.5) years for the 28 children (and 29 eyes) with clinical imaging results, and 24 (86%) were boys. A comparison between imaging modalities revealed OCT features that were not visible in photographs or FA, including exudates in multiple retinal layers (23 [82.1%]), small pockets of subretinal fluid (4 [14.3%]), an outer retinal atrophy overlying fibrotic nodules (7 [25.0%]), and small preretinal hyperreflective OCT dots (25 [89.3%]). Next, a comparison with light micrographs introduced an association of OCT findings with possible pathological features, including hyperreflective linear structures on OCT that appeared consistent with cholesterol crystals, small hyperreflective dots with macrophages, outer retinal tubulations with rosettes, and analogous OCT histopathology features such as intraretinal vessels entering fibrotic nodules and retinal pigment epithelium excrescences under the subretinal fluid. An OCT analysis revealed intraretinal cystoid spaces in 19 eyes, but in 9 of 19 (47.4) this was not associated with cystoid macular leakage; rather, fluorescein leakage was observed from peripheral telangiectatic vessels. Additionally, exudates were intraretinal only (6 [21.4%]) or both intraretinal and subretinal (17 [60.7%]); none were subretinal only. In eyes with follow-up results, new fibrosis developed in 8 of 17 eyes (47.1%). Fibrosis developed in 5 of 5 eyes (100%) with baseline subretinal fluid vs 3 of 12 without (25%; 95% CI, 22%-92%) and in 7 of 9 eyes (77.8%) with subretinal exudates vs 1 of 8 (12.5%) without (95% CI, 16%-89%).

Conclusions And Relevance: Optical coherence tomography may show the transient and permanent effects of Coats disease on the retina. These results suggest that exudates and fluid in the macular subretinal space appear later in the disease and may result in fibrosis formation. Further studies are needed to confirm if early treatment could prevent vision-threatening macular fibrosis.
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http://dx.doi.org/10.1001/jamaophthalmol.2018.5654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439851PMC
February 2019