Publications by authors named "Eric Nudleman"

48 Publications

Patterns and Predictors of Successful Treatment Discontinuation in Retinal Vein Occlusions With Macular Edema in the Real World.

Ophthalmic Surg Lasers Imaging Retina 2021 Feb;52(2):84-92

Background And Objective: To identify factors associated with successful treatment discontinuation in eyes with retinal vein occlusions (RVOs) and macular edema (ME) in real-world settings.

Patients And Methods: Retrospective study of 214 eyes with RVO and ME with 24-month follow-up at five academic centers. Regression analyses identified factors associated with (1) successful treatment discontinuation for at least 6 months without fluid recurrence and (2) best-corrected visual acuity (BCVA) at 24 months.

Results: Forty percent of eyes with branch RVO and 35% with central RVO (CRVO) / hemi-retinal RVO (HRVO) successfully discontinued therapy without fluid recurrence, with median time to discontinuation of 6 and 7 months, respectively. Lower 6-month central subfield thickness was associated with greater likelihood of treatment discontinuation within 24 months for eyes with CRVO/HRVO (P = .001), whereas better 6-month BCVA was associated with better 24-month BCVA for all RVO subtypes (P < .001).

Conclusion: Early anatomic response at 6 months is associated with greater likelihood of stopping treatments. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:84-92.].
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http://dx.doi.org/10.3928/23258160-20210201-05DOI Listing
February 2021

The Best Course of Action.

Surv Ophthalmol 2021 Jan 29. Epub 2021 Jan 29.

Shiley Eye Institute, Rady Childrens Hospital, University of California, San Diego, CA.

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http://dx.doi.org/10.1016/j.survophthal.2021.01.013DOI Listing
January 2021

Traumatic Retinal Detachment in Patients with Self-Injurious Behavior: An International Multicenter Study.

Ophthalmol Retina 2020 Nov 22. Epub 2020 Nov 22.

Wills Eye Hospital, Mid Atlantic Retina, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address:

Purpose: To describe the clinical characteristics, surgical outcomes, and management recommendations in patients with traumatic rhegmatogenous retinal detachment (RRD) resulting from self-injurious behavior (SIB).

Design: International, multicenter, retrospective, interventional case series.

Participants: Patients with SIB from 23 centers with RRD in at least 1 eye.

Methods: Clinical histories, preoperative assessment, surgical details, postoperative management, behavioral intervention, and follow-up examination findings were reviewed.

Main Outcome Measures: The rate of single-surgery anatomic success (SSAS) was the primary outcome. Other outcomes included new RRD in formerly attached eyes, final retinal reattachment, and final visual acuity.

Results: One hundred seven eyes with RRDs were included from 78 patients. Fifty-four percent of patients had bilateral RRD or phthisis bulbi in the fellow eye at final follow-up. The most common systemic diagnoses were autism spectrum disorder (35.9%) and trisomy 21 (21.8%) and the most common behavior was face hitting (74.4%). The average follow-up time was 3.3 ± 2.8 years, and surgical outcomes for operable eyes were restricted to patients with at least 3 months of follow-up (81 eyes). Primary initial surgeries were vitrectomy alone (33.3%), primary scleral buckle (SB; 26.9%), and vitrectomy with SB (39.7%), and 5 prophylactic SBs were placed. Twenty-three eyes (21.5%) with RRDs were inoperable. The SSAS was 23.1% without tamponade (37.2% if including silicone oil), and final reattachment was attained in 80% (36.3% without silicone oil tamponade). Funnel-configured RRD (P = 0.006) and the presence of grade C proliferative vitreoretinopathy (P = 0.002) correlated with re-detachment. The use of an SB predicted the final attachment rate during the initial surgery (P = 0.005) or at any surgery (P = 0.008. These associations held if restricting to 64 patients with ≥12 months followup. Anatomic reattachment correlated with better visual acuity (P < 0.001).

Conclusions: RRD resulting from SIB poses therapeutic challenges because of limited patient cooperation, bilateral involvement, chronicity, and ongoing trauma in vulnerable and neglected patients. The surgical success rates were some of the lowest in the modern retinal detachment literature. The use of an SB may result in better outcomes, and visual function can be restored in some patients.
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http://dx.doi.org/10.1016/j.oret.2020.11.012DOI Listing
November 2020

Multimodal Imaging of Idiopathic Fovea Plana.

Ophthalmol Retina 2020 10;4(10):972

Shiley Eye Institute, Department of Ophthalmology, University of California San Diego, San Diego, California.

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http://dx.doi.org/10.1016/j.oret.2020.04.020DOI Listing
October 2020

Evaluation of the clinical utility of optical coherence tomography angiography in age-related macular degeneration.

Br J Ophthalmol 2020 Aug 21. Epub 2020 Aug 21.

Jacobs Retina Center, Shiley Eye, UCSD, La Jolla, California, USA

Background/aims: To evaluate the ability of optical coherence tomography angiography (OCTA) to identify the presence or absence of choroidal neovascularisation (CNV) and CNV activity in age-related macular degeneration (AMD).

Methods: Clinical parameters, fundus fluorescein angiogram and spectral-domain optical coherence tomography (SD-OCT) were used as the gold standard to determine disease activity. OCTA imaging was performed on the same day and was graded by two masked retina specialists for the presence or absence of CNV. Traditional multimodal imaging and OCTA findings were compared.

Results: One hundred and fifty-two eyes of 106 patients with AMD were retrospectively reviewed. Of these, 59 eyes had wet AMD and 93 had dry AMD with high-risk drusen. OCTA had 85.4% and 79.3% specificity and sensitivity, respectively, in determining the presence or absence of CNV. OCTA was 69.5% accurate in determining active CNV. False positives and negatives were 21.6% and 8.0%, respectively.

Conclusions: This study suggests that en-face OCTA images allow a moderate ability to identify CNV and that OCTA alone is weak at recognising active CNV requiring treatment in AMD.
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http://dx.doi.org/10.1136/bjophthalmol-2020-316622DOI Listing
August 2020

Late-Onset Retinal Findings and Complications in Untreated Retinopathy of Prematurity.

Ophthalmol Retina 2020 06 24;4(6):602-612. Epub 2019 Dec 24.

Retina and Vitreous of Texas, Houston, Texas. Electronic address:

Purpose: To investigate late retinal findings and complications of eyes with a history of retinopathy of prematurity (ROP) that did not meet treatment criteria and did not receive treatment during infancy.

Design: Retrospective, nonconsecutive, noncomparative, multicenter case series.

Participants: Three hundred sixty-three eyes of 186 patients.

Methods: Data were requested from multiple providers on premature patients with a history of ROP and no treatment during infancy who demonstrated late retinal findings or complications and included age, gender, gestational age and weight, zone and stage at infancy, visual acuity, current retina vascularization status, vitreous character, presence of peripheral retinal findings such as lattice retinal tears and detachments (RDs), retinoschisis, and fluorescein findings.

Main Outcome Measures: Rate of RDs and factors conferring a higher risk of RDs.

Results: The average age was 34.5 years (range, 7-76 years), average gestational age was 26.6 weeks (range, 23-34 weeks), and average birth weight was 875 g (range, 425-1590 g). Findings included lattice in 196 eyes (54.0%), atrophic holes in 126 eyes (34.7%), retinal tears in 111 eyes (30.6%), RDs in 140 eyes (38.6 %), tractional retinoschisis in 44 eyes (11.9%), and visible vitreous condensation ridge-like interface in 112 eyes (30.5%). Fluorescein angiography (FA) was performed in 113 eyes, of which 59 eyes (52.2%) showed leakage and 16 eyes (14.2%) showed neovascularization. Incomplete vascularization posterior to zone 3 was common (71.6% of eyes). Retinal detachments were more likely in patients with a gestational age of 29 weeks or less (P < 0.05) and in eyes with furthest vascularization to posterior zone 2 eyes compared with zone 3 eyes (P = 0.009).

Conclusions: Eyes with ROP not meeting the treatment threshold during infancy showed various late retinal findings and complications, of which RDs were the most concerning. Complications were seen in all age groups, including patients born after the Early Treatment for Retinopathy of Prematurity Study. Contributing factors to RDs included atrophic holes within peripheral avascular retina, visible vitreous condensation ridge-like interface with residual traction, and premature vitreous syneresis. We recommend regular examinations and consideration of ultra-widefield FA examinations. Prospective studies are needed to explore the frequency of complications and benefit of prophylactic treatment and if eyes treated with anti-vascular endothelial growth factor therapy are at risk of similar findings and complications.
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http://dx.doi.org/10.1016/j.oret.2019.12.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282927PMC
June 2020

Comparison of Digital Widefield Retinal Imaging With Indirect Ophthalmoscopy in Pediatric Patients.

Ophthalmic Surg Lasers Imaging Retina 2019 09;50(9):580-585

Background And Objective: Approximately 16,000 children in the United States lose vision each year because of retinal disease. The authors compare digital ultra-widefield (UWF) photography to indirect ophthalmoscopy in children.

Patients And Methods: Prospective, single-center study of patients ages 3 to 17 years. Retinal area during indirect ophthalmoscopy was compared with retinal area in digital UWF fundus photographs. Image quality was graded. A survey to assess the usefulness of the retinal image was obtained.

Results: The retinal area (mean ± standard deviation, mm) evaluated with indirect ophthalmoscopy was 413 ± 194 mm, compared with 652 ± 117 mm with widefield photography (P < .001). The difference was largest in children younger than 14. Image quality was significantly associated with patient cooperation.

Conclusions: High-quality UWF photographs evaluate more peripheral retina than the in-office dilated funduscopic exam in children under 14. Photography assisted with family counseling in 17% of patients and the avoidance of examination under anesthesia in 2% of patients. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:580-585.].
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http://dx.doi.org/10.3928/23258160-20190905-07DOI Listing
September 2019

Emerging Insights and Interventions for Diabetic Retinopathy.

Curr Diab Rep 2019 09 10;19(10):100. Epub 2019 Sep 10.

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 660 S. Euclid Ave. 8096, St. Louis, MO, 63108, USA.

Purpose Of Review: To introduce recent advances in the understanding of diabetic retinopathy and to summarize current and emerging strategies to treat this common and complex cause of vision loss.

Recent Findings: Advances in retinal imaging and functional analysis indicate that retinal vascular and neural pathologies exist long before the development of clinically visible retinopathy. Such diagnostics could facilitate risk stratification and selective early intervention in high-risk patients. Antagonists of the vascular endothelial growth factor pathway effectively reduce vision loss in diabetes and promote regression of disease severity. Promising new strategies to treat diabetic retinopathy involve novel systemic diabetes therapy and ocular therapies that antagonize angiogenic growth factor signaling, improve blood-retina barrier function and neurovascular coupling, modulate neuroretinal metabolism, or provide neuroprotection. Long considered a pure microvasculopathy, diabetic retinopathy in fact affects the neural and vascular retina as well as neurovascular communication. Emerging therapies include those that target neuroretinal dysfunction in addition to those modulating vascular biology.
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http://dx.doi.org/10.1007/s11892-019-1218-2DOI Listing
September 2019

Correlating Changes in the Macular Microvasculature and Capillary Network to Peripheral Vascular Pathologic Features in Familial Exudative Vitreoretinopathy.

Ophthalmol Retina 2019 07 4;3(7):597-606. Epub 2019 Mar 4.

Department of Ophthalmology, Shiley Eye Institute and Jacobs Retina Center, University of California, San Diego, La Jolla, California. Electronic address:

Purpose: To evaluate the macular microvasculature in patients with familial exudative vitreoretinopathy (FEVR) using OCT angiography (OCTA) and to assess for peripheral vascular changes using widefield fluorescein angiography (WFA).

Design: Multicenter, retrospective, comparative, observational case series.

Participants: We identified 411 patients with FEVR, examined between September 2014 and June 2018. Fifty-seven patients with FEVR and 60 healthy controls had OCTA images of sufficient quality for analysis.

Methods: Custom software was used to assess for layer-specific, quantitative changes in vascular density and morphologic features on OCTA by way of vessel density (VD), skeletal density (SD), fractal dimension (FD), vessel diameter index (VDI), and foveal avascular zone (FAZ). Widefield fluorescein angiography images were reviewed for peripheral vascular changes including capillary dropout, late-phase angiographic posterior and peripheral vascular leakage (LAPPEL), vascular dragging, venous-venous shunts, and arteriovenous shunts.

Main Outcome Measures: Macular microvascular parameters on OCTA and peripheral angiographic findings on WFA.

Results: OCT angiography analysis of 117 patients (187 eyes; 92 FEVR patients and 95 control participants) demonstrated significantly reduced VD, SD, and FD and greater VDI in patients with FEVR compared with controls in the nonsegmented retina, superficial retinal layer (SRL), and deep retinal layer (DRL). The FAZ was larger compared with that in control eyes in the DRL (P < 0.0001), but not the SRL (P = 0.52). Subanalysis by FEVR stage showed the same microvascular changes compared with controls for all parameters. Widefield fluorescein angiography analysis of 95 eyes (53 patients) with FEVR demonstrated capillary nonperfusion in all eyes: 47 eyes (49.5%) showed LAPPEL, 32 eyes (33.7%) showed vascular dragging, 30 eyes (31.6%) had venous-venous shunts, and 33 eyes (34.7%) had arteriovenous shunts. Decreasing macular VD on OCTA correlated with increasing peripheral capillary nonperfusion on WFA. Decreasing fractal dimension on OCTA correlated with increasing LAPPEL severity on WFA.

Conclusions: Patients with FEVR demonstrated abnormalities in the macular microvasculature and capillary network, in addition to the peripheral retina. The macular microvascular parameters on OCTA may serve as biomarkers of changes in the retinal periphery on WFA.
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http://dx.doi.org/10.1016/j.oret.2019.02.013DOI Listing
July 2019

Foveal Avascular Zone Distortion in Epiretinal Membrane by Optical Coherence Tomography Angiography.

Ophthalmic Surg Lasers Imaging Retina 2019 05;50(5):295-301

Background And Objective: To show the morphologic changes on the foveal avascular zone (FAZ) in patients with epiretinal membrane (ERM) using optical coherence tomography angiography (OCTA) and to demonstrate the correlation between distortion of FAZ and features of the ERM.

Patients And Methods: FAZ eccentricity index (longest diameter of FAZ/shortest diameter of FAZ) was measured in 52 patients with ERM and compared with 27 healthy subjects' values. The density of the ERM was quantified using a grading scale (0-3) on multicolor scanning laser images, and spectral-domain OCT characteristics of the eyes were assessed.

Results: Of the 52 eyes with ERM, 31 eyes (59.61%) showed some foveal remodeling, including full (13.46%) or partial (30.76%) apparent vascularization of FAZ, presence of a vessel crossing the fovea (9.61%), and horizontal or vertical elongation of FAZ (5.76%). The mean FAZ eccentricity index was 0.84 ± 0.46 (range: 0.0-1.86) in eyes with ERM and 0.98 ± 0.07 (range: 0.96-1.02) in the control subjects, respectively (P = .02). There was a negative significant correlation between FAZ eccentricity index and central macular thickness (P = .04).

Conclusions: Thickening of the central fovea leads to foveal remodeling in ERM eyes, and OCTA enables the visualization of architectural FAZ changes. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:295-301.].
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http://dx.doi.org/10.3928/23258160-20190503-06DOI Listing
May 2019

Ocular Hypertension in Adults with a History of Prematurity.

Ophthalmol Retina 2018 06 1;2(6):629-635. Epub 2017 Dec 1.

Associated Retinal Consultants P.C., Royal Oak, Michigan; Oakland University William Beaumont School of Medicine, Department of Ophthalmology, Royal Oak, Michigan. Electronic address:

Purpose: To determine the ocular hypertension (OHT) incidence in patients with a history of prematurity and the effect of intervention for acute retinopathy of prematurity (ROP) in infancy on OHT incidence.

Design: Retrospective case series at a single tertiary referral vitreoretinal practice.

Participants: A total of 407 eyes of 213 patients were included, with ROP stage 0 to 5.

Methods: A retrospective chart review was conducted of patients aged ≥15 years, seen from 1973 to 2013, with a history of premature birth (gestational age <32 weeks). Data were collected from patient charts, including gender, date of birth, gestational age at birth, birth weight, stage of ROP at presentation, management (including laser, cryotherapy, lens-sparing vitrectomy [LSV], or lensectomy-vitrectomy). Ocular hypertension (if present) data included age of onset, timing of glaucoma surgery (if performed), lens status, and last follow-up examination.

Main Outcome Measures: Development of OHT, defined as eyes requiring a glaucoma medication for more than 6 consecutive months or surgical intervention for elevated intraocular pressure.

Results: Of included eyes, 155 (38.1%) developed OHT within 69 years of follow-up. Subgroup analyses revealed an OHT incidence of 23.2% (36/155 eyes) in eyes without a history of any treatment for acute ROP (spontaneously regressed), 23.3% (10/43 eyes) in eyes that underwent ablative therapy alone, and 58.5% (76/130 eyes) in eyes requiring acute incisional retinal surgery (P < 0.01). Stage 4 eyes had a lower OHT incidence compared with stage 5 eyes (40.5% [17/42] vs. 66.7% [54/81], P < 0.01); however, among stage 4 and stage 5 eyes, phakic eyes at last follow-up had a decreased OHT incidence compared with aphakic eyes (27.8% [5/18] vs. 69.8% [60/86], P < 0.01).

Conclusions: Patients with a history of extreme prematurity are at an increased risk of OHT and glaucoma, even if they did not receive acute ROP treatment. More severe acute ROP is associated with higher incidence of OHT, and this is associated with an increased incidence of incisional surgical intervention. Awareness of the increased lifelong risk of adverse ocular sequelae in patients with a history of prematurity will help guide appropriate monitoring.
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http://dx.doi.org/10.1016/j.oret.2017.10.005DOI Listing
June 2018

Microcornea, Posterior Megalolenticonus, Persistent Fetal Vasculature, and Coloboma Syndrome Associated With a New Mutation in ZNF408.

Ophthalmic Surg Lasers Imaging Retina 2019 04;50(4):253-256

The authors report a case of a 6-week-old girl with microphthalmia, posterior lenticonus, persistent fetal vasculature, and coloboma of the right eye, with morning glory disc anomaly and falciform retinal folds of the left eye. Genetic testing revealed a previously unreported mutation (c.1471A>G [p.T491A]) in the gene ZNF408, which has been associated with autosomal recessive retinitis pigmentosa and autosomal dominant familial exudative vitreoretinopathy. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:253-256.].
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http://dx.doi.org/10.3928/23258160-20190401-10DOI Listing
April 2019

Longitudinal Examination of Fellow-Eye Vascular Anomalies in Coats' Disease With Widefield Fluorescein Angiography: A Multicenter Study.

Ophthalmic Surg Lasers Imaging Retina 2019 04;50(4):221-227

Background And Objective: Retinovascular anomalies in the fellow eyes of patients with Coats' disease have been described, but the clinical significance is unknown, as well as whether these lesions progress over time.

Patients And Methods: This is an international, multicenter, retrospective, observational cohort study of fellow-eye abnormalities on widefield fluorescein angiography in patients with Coats' disease.

Results: Three hundred fifty eyes of 175 patients with Coats' disease were analyzed. A total of 33 patients (18.8%) demonstrated abnormal fellow-eye findings: 14 (42.4%) telangiectasias, 18 (54.5%) aneurysms, six (18.2%) segmental non-perfusion, six (18.2%) leakage, and two (6.0%) vascular tortuosity. All eyes were asymptomatic, and none of the lesions progressed over time. There was no association between fellow-eye findings with severity of Coats' disease (P = .16), patient age (P = .16), or presence of systemic vascular disease (P = .16).

Conclusions: The vascular abnormalities in fellow eyes of patients with Coats' disease did not progress over time. Observation is a reasonable initial management strategy. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:221-227.].
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http://dx.doi.org/10.3928/23258160-20190401-04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615457PMC
April 2019

Pneumatic Retinopexy Experience and Outcomes of Vitreoretinal Fellows in the United States: A Multicenter Study.

Ophthalmol Retina 2019 02 20;3(2):140-145. Epub 2018 Sep 20.

Department of Ophthalmology & Vision Science, University of California, Davis, Sacramento, CA.

Objective: To evaluate the outcomes of patients undergoing pneumatic retinopexy (PR) performed by vitreoretinal fellows at 6 academic centers in the United States.

Design: Retrospective, multicenter, consecutive case series.

Participants: 483 patients with primary retinal detachments who underwent PR by 49 vitreoretinal fellows from 6 U.S. training sites between 2002 and 2016.

Methods: We reviewed medical records of patients and recorded baseline clinical characteristics (age, sex, baseline visual acuity, lens status, presence of lattice degeneration, presence of vitreous hemorrhage, location of retinal breaks, macular status, and size of detachment), visual and anatomic outcomes at 3-months after PR, as well as training level and PR experience of the fellow at the time of the procedure.

Main Outcome Measures: Single-procedure anatomic success and visual acuity at 3-months follow-up, and association with clinical and training-related factors.

Results: Vitreoretinal fellows performed a variable number of PR, with a median of 7 cases per fellow (range 1-24). Single-procedure anatomic success was 66.8%, and mean LogMAR visual outcome was 0.43 (Snellen equivalent 20/54) at 3 months. Factors that were independently associated with single-procedure success include phakic lens status (P = 0.01), smaller size of retinal detachment (P = 0.02), and the fellow's procedure experience (P = 0.01). The only factor associated with worse visual outcome was baseline visual acuity (P < 0.001).

Conclusion: Vitreoretinal fellows perform variably few pneumatic retinopexies but have outcomes comparable to reported rates by experienced specialists. Procedure experience of individual fellows may impact anatomic outcomes.
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http://dx.doi.org/10.1016/j.oret.2018.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435286PMC
February 2019

Time Requirements of Paper-Based Clinical Workflows and After-Hours Documentation in a Multispecialty Academic Ophthalmology Practice.

Am J Ophthalmol 2019 10 22;206:161-167. Epub 2019 Mar 22.

Department of Biomedical Informatics, University of California San Diego, La Jolla, California; Department of Medicine, University of California San Diego, La Jolla, California; Division of Health Services Research and Development, Veterans Administration San Diego Healthcare System, La Jolla, California.

Purpose: To assess time requirements for patient encounters and estimate after-hours demands of paper-based clinical workflows in ophthalmology.

Design: Time-and-motion study with a structured survey.

Methods: This study was conducted in a single academic ophthalmology department. A convenience sample consisted of 7 attending ophthalmologists from 6 subspecialties observed during 414 patient encounters for the time-motion analysis and 12 attending ophthalmologists for the survey. Outcome measurements consisted of total time spent by attending ophthalmologists per patient and time spent on documentation, examination, and talking with patients. The survey assessed time requirements of documentation-related activities performed outside of scheduled clinic hours.

Results: Among the 7 attending ophthalmologists observed (6 men and 1 woman), mean ± SD age 43.9 ± 7.1 years, during encounters with 414 patients (57.8 ± 24.6 years of age), total time spent per patient was 8.1 ± 4.8 minutes, with 2.8 ± 1.4 minutes (38%) for documentation, 1.2 ± 0.9 minutes (17%) for examination, and 3.3 ± 3.1 minutes (37%) for talking with patients. New patient evaluations required significantly more time than routine follow-up visits and postoperative visits. Higher clinical volumes were associated with less time per patient. Survey results indicated that paper-based documentation was associated with minimal after-hours work on weeknights and weekends.

Conclusions: Paper-based documentation takes up a substantial portion of the total time spent for patient care in outpatient ophthalmology clinics but is associated with minimal after-hours work. Understanding paper-based clinical workflows may help inform targeted strategies for improving electronic health record use in ophthalmology.
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http://dx.doi.org/10.1016/j.ajo.2019.03.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755078PMC
October 2019

Quantification of Retinal Nonperfusion Associated With Posterior Segment Neovascularization in Diabetic Retinopathy Using Ultra-Widefield Fluorescein Angiography.

Ophthalmic Surg Lasers Imaging Retina 2019 02;50(2):86-92

Background And Objective: To quantify the size and location of nonperfusion associated with posterior segment neovascularization (NV) in proliferative diabetic retinopathy (PDR) using ultra-widefield fluorescein angiography.

Patients And Methods: Cross-sectional study of 18 eyes with PDR. The total image area, areas of nonperfusion, buds of posterior segment neovascularization (either neovascularization of the disc or elsewhere), and the distances from each bud to the nearest area of nonperfusion and to the disc were measured.

Results: Nonperfused areas with associated neovascularization were significantly larger than areas without neovascularization (32.0% ± 5.24% of the retinal image vs. 3.3% ± 0.92%; P < .001) and were more likely to be posteriorly located. Nonperfusion encompassing greater than 23% of the total angiographic image had more associated neovascular buds (9.64 ± 2.16 vs. 0.86 ± 0.29; P < .0001), which were closer to the disc (7.53 mm ± 0.27 mm vs. 9.24 mm ± 0.64 mm; P = .014).

Conclusion: A threshold size of nonperfusion greater than 23% of the retinal image is associated with posterior segment neovascularization and may serve as an indicator of risk for the development of PDR. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:86-92.].
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http://dx.doi.org/10.3928/23258160-20190129-04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501581PMC
February 2019

Reply.

Ophthalmology 2019 01;126(1):e4-e5

Associated Retinal Consultants, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan.

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http://dx.doi.org/10.1016/j.ophtha.2018.07.021DOI Listing
January 2019

Interleukin-22 promotes tumor angiogenesis.

Angiogenesis 2019 05 11;22(2):311-323. Epub 2018 Dec 11.

Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA.

T17 cells play important yet complex roles in cancer development and progression. We previously reported that T17 cells and IL-17 mediate resistance to anti-VEGF therapy by inducing recruitment of immunosuppressive and proangiogenic myeloid cells to the tumor microenvironment. Here, we demonstrate that IL-22, a key effector cytokine expressed by T17 cells, directly acts on endothelial cells to promote tumor angiogenesis. IL-22 induces endothelial cell proliferation, survival, and chemotaxis in vitro and neovascularization in an ex vivo mouse choroid explant model. Blockade of IL-22, with a neutralizing antibody, significantly inhibits tumor growth associated with reduced microvascular density. No synergistic effect of IL-22 with VEGF was observed. These results identify IL-22 as a potential therapeutic target for blocking tumor angiogenesis.
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http://dx.doi.org/10.1007/s10456-018-9658-xDOI Listing
May 2019

ANATOMICAL AND FUNCTIONAL TESTING IN DIABETIC PATIENTS WITHOUT RETINOPATHY: Results of Optical Coherence Tomography Angiography and Visual Acuity Under Varying Contrast and Luminance Conditions.

Retina 2019 Oct;39(10):2022-2031

Department of Ophthalmology, Jacobs Retina Center, Shiley Eye Institute, University of California San Diego, La Jolla, California.

Purpose: To assess early retinal microvascular and functional changes in diabetic patients without clinical evidence of diabetic retinopathy with optical coherence tomography angiography and central visual analyzer.

Methods: This was an observational case-control study of diabetic patients without diabetic retinopathy and nondiabetic controls. Patients underwent optical coherence tomography angiography imaging and visual acuity testing using the central visual analyzer. The foveal avascular zone area and the capillary density in the superficial and deep capillary plexuses were measured manually by a masked grader.

Results: Sixty eyes from 35 diabetic patients were included in the study group, and 45 eyes from 31 nondiabetic patients were included in the control group. The foveal avascular zone area was not significantly different between the diabetic group and controls (both P > 0.05). The mean capillary density in the deep capillary plexus was significantly lower in diabetic eyes compared with control eyes (P = 0.04). The mean visual acuity in all central visual analyzer modules was significantly decreased in diabetic patients compared with controls (all P < 0.05).

Conclusion: Optical coherence tomography angiography was able to detect retinal microvascular changes in the deep capillary plexus, and the central visual analyzer showed signs of decreased visual acuity under conditions simulating suboptimal contrast and glare in diabetic patients without diabetic retinopathy.
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http://dx.doi.org/10.1097/IAE.0000000000002258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330253PMC
October 2019

RESOLUTION, DEPTH OF FIELD, AND PHYSICIAN SATISFACTION DURING DIGITALLY ASSISTED VITREORETINAL SURGERY.

Retina 2019 Sep;39(9):1768-1771

Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, California.

Purpose: To evaluate depth of field, lateral resolution, and image quality of a heads-up 3D visualization system for vitreoretinal surgery using physician survey and optical measurement outcomes.

Methods: Depth of field and lateral resolution were compared between the standard ocular viewing system and the digital 3D system at ×5, ×13, and ×18 magnification by 6 retinal surgeons. Optical techniques were used as well as a survey of surgeon impression. Surgeon impression surveys were performed after 6 weeks of surgical use of the device.

Results: Physician questionnaire survey scores for depth of field at high magnification were better for the digital 3D system and equivalent for all other categories. Measured lateral resolution was 36.7 mm and 16.6 mm at ×5 magnification (P < 0.001), 14.3 mm and 6.4 mm at ×13 magnification (P < 0.001), and 9.8 mm and 4.2 mm (P < 0.001) at ×18 magnification for the digital 3D and oculars, respectively. Measured depth of field was 4.00 mm and 6.78 mm at ×5 magnification (P = 0.027), 0.72 mm and 0.86 mm at ×13 (P = 0.311), and 0.28 mm and 0.40 mm at ×18 magnification (P = 0.235) for the oculars and digital 3D, respectively.

Conclusion: Lateral resolution of the digital 3D system was half that of the ocular viewing system and there was some improvement in depth of field with the digital system. Surgeon impression suggested that the digital system was superior when evaluating depth of field at high magnification.
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http://dx.doi.org/10.1097/IAE.0000000000002236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310113PMC
September 2019

WNT7A/B promote choroidal neovascularization.

Exp Eye Res 2018 09 1;174:107-112. Epub 2018 Jun 1.

Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA; Diabetic Cardiovascular Disease Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA. Electronic address:

Perturbations in WNT signaling are associated with congenital eye disorders, including familial exudative vitreoretinopathy and Norrie disease. More recently, activation of the WNT pathway has also been shown to be associated with age-related macular degeneration (AMD). In this study, we identified that in choroidal neovascular membranes from AMD patients, β-catenin is activated specifically in the vascular endothelium, suggesting that WNT promotes pathologic angiogenesis by directly affecting vascular endothelial cells. WNT7B has been shown to be important during eye development for regression of the fetal hyaloid vasculature. However, it has not yet been established whether WNT7A and/or WNT7B are involved in neovascular AMD pathogenesis. Here, we show that WNT7A and WNT7B increase the proliferation of human dermal microvascular endothelial cells in a dose-dependent manner. Both WNT7A and WNT7B also stimulated vascular sprouting from mouse choroidal explants in vitro. To evaluate in vivo relevance, we generated mice systemically deficient in Wnt7a and/or Wnt7b. Genetic deletion of both Wnt7a and Wnt7b decreased the severity of laser injury-induced choroidal neovascularization (CNV), while individual deletion of either Wnt7a or Wnt7b did not have a significant effect on CNV, suggesting that WNT7A and WNT7B have redundant pro-angiogenic roles in vivo. Cumulatively, these findings identify specific WNT isoforms that may play a pathologic role in CNV as observed in patients with neovascular AMD. Although the source of increased WNT7A and/or WNT7B in CNV requires further investigation, WNT signaling may be a potential target for therapeutic intervention if these results are demonstrated to be relevant in human disease.
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http://dx.doi.org/10.1016/j.exer.2018.05.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110966PMC
September 2018

Animal Models of Proliferative Vitreoretinopathy and Their Use in Pharmaceutical Investigations.

Ophthalmic Res 2018 3;60(4):195-204. Epub 2018 May 3.

Department of Ophthalmology and Shiley Eye Institute, University of California, San Diego, California, USA.

Animal models are indispensable for pharmaceutical investigations. However, investigators often have difficulty choosing the appropriate modal for their research. To provide a comprehensive and convenient source of information about animal models of proliferative vitreoretinopathy (PVR), the current review sorted and analyzed representative animal models for pharmacotherapy of PVR since 1976.
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http://dx.doi.org/10.1159/000488492DOI Listing
February 2019

COMPARISON OF RETINAL PATHOLOGY VISUALIZATION IN MULTISPECTRAL SCANNING LASER IMAGING.

Retina 2019 Jul;39(7):1333-1342

Department of Ophthalmology, Jacobs Retina Center at Shiley Eye Institute, University of California San Diego, La Jolla, California.

Purpose: To compare retinal pathology visualization in multispectral scanning laser ophthalmoscope imaging between the Spectralis and Optos devices.

Methods: This retrospective cross-sectional study included 42 eyes from 30 patients with age-related macular degeneration (19 eyes), diabetic retinopathy (10 eyes), and epiretinal membrane (13 eyes). All patients underwent retinal imaging with a color fundus camera (broad-spectrum white light), the Spectralis HRA-2 system (3-color monochromatic lasers), and the Optos P200 system (2-color monochromatic lasers). The Optos image was cropped to a similar size as the Spectralis image. Seven masked graders marked retinal pathologies in each image within a 5 × 5 grid that included the macula.

Results: The average area with detected retinal pathology in all eyes was larger in the Spectralis images compared with Optos images (32.4% larger, P < 0.0001), mainly because of better visualization of epiretinal membrane and retinal hemorrhage. The average detection rate of age-related macular degeneration and diabetic retinopathy pathologies was similar across the three modalities, whereas epiretinal membrane detection rate was significantly higher in the Spectralis images.

Conclusion: Spectralis tricolor multispectral scanning laser ophthalmoscope imaging had higher rate of pathology detection primarily because of better epiretinal membrane and retinal hemorrhage visualization compared with Optos bicolor multispectral scanning laser ophthalmoscope imaging.
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http://dx.doi.org/10.1097/IAE.0000000000002156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6139284PMC
July 2019

Sutureless transscleral fixation of secondary intraocular lenses.

Curr Opin Ophthalmol 2018 May;29(3):210-216

Department of Ophthalmology, Rutgers Robert Wood Johnson Medical School.

Purpose Of Review: The surgical approach to eyes needing a secondary intraocular lens have evolved rapidly in recent years. Here, we will focus on techniques for scleral-fixation of intraocular lenses (IOLs), and will review the evidence for their safety and efficacy.

Recent Findings: Transscleral fixation of IOLs refers the placement of lens haptics within scleral tunnels to stabilize the lens in eyes that lack adequate capsular support. Various surgical techniques have been reported recently to accomplish this goal. These include the use of a trocar, microvitreoretinal blade, or hypodermic needle to create the scleral tunnels, as well as several methods for placing the haptics through the tunnels. Although long-term data is lacking, each technique has been shown to have good visual outcomes without significant side effects.

Summary: Surgical approaches for the transscleral fixation of secondary IOLs provide a safe and effective technique for the management of eyes with insufficient capsular support.
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http://dx.doi.org/10.1097/ICU.0000000000000474DOI Listing
May 2018

IDENTIFICATION OF FACTORS RELATED TO SUBFOVEAL DETACHMENT SECONDARY TO EPIRETINAL MEMBRANE.

Retina 2019 May;39(5):988-998

Department of Ophthalmology, Jacobs Retina Center, Shiley Eye Institute, University of California San Diego, La Jolla, California.

Purpose: To demonstrate factors related to the presence of subfoveal detachment (SD) secondary to epiretinal membrane (ERM) and to characterize the predictors for the resolution of SD after membrane peeling.

Methods: A retrospective chart review was conducted for the patients who underwent pars plana vitrectomy for the idiopathic ERM peeling. Preoperative spectral domain optical coherence tomography characteristics of the eyes including central foveal thickness, foveal center point thickness, presence of intraretinal cyst, continuity of the membrane, area of the membrane within fovea (1 mm), and entire macula (6 mm) were evaluated to find the best predictors for the presence of SD. These predictors as well as perioperative parameters including use of internal tamponade and volume of SD were considered for time of resolution of SD.

Results: Of 158 included eyes, 20.2% eyes (32 eyes) had SD, and the presence of SD was significantly related to involvement of the membrane within the macula. After surgery, SD completely resolved in 90.6% of eyes (29 eyes) at a median of 2.97 months (range: 0.03-12.0 months). The area of the membrane within fovea was the only significant predictor for time to resolution of SD (hazard ratio = 1.20, 95% confidence interval = 1.100-1.324, P = 0.021). A small percent of eyes showed some further changes including fluctuation (6.2%) or persistence (3.1%) of fluid.

Conclusion: A larger extension of ERM over the macula is related to higher likelihood of the presence of SD. Time for resolution of subfoveal detachment does not seem to be affected by the preoperative and perioperative factors except the extent of membrane within 1,000 μm of the fovea.
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http://dx.doi.org/10.1097/IAE.0000000000002056DOI Listing
May 2019

Glaucoma after Lens-Sparing Vitrectomy for Advanced Retinopathy of Prematurity.

Ophthalmology 2018 05 11;125(5):671-675. Epub 2017 Dec 11.

Associated Retinal Consultants, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan. Electronic address:

Purpose: To report the incidence of, and factors related to, glaucoma after lens-sparing vitrectomy (LSV) surgery in advanced retinopathy of prematurity (ROP).

Design: Retrospective case series at a single tertiary referral pediatric vitreoretinal practice.

Participants: Four hundred and one eyes from 270 patients were included.

Methods: The medical records of patients who underwent LSV for stage 4A, 4B, and 5 ROP were retrospectively reviewed. Data were collected from patient charts including gender, gestational age at birth, birthweight, stage of ROP at presentation, prior treatment (laser or cryotherapy), subsequent retinal surgeries, presence of glaucoma, time to glaucoma (interval between LSV and the onset of glaucoma), date of lensectomy (if performed), and retinal attachment status at last visit. Lensectomy was considered as a time-dependent covariate in the analysis.

Main Outcome Measures: Incidence of glaucoma and potential risk factors for time to glaucoma.

Results: Among 401 eyes with advanced ROP, 40 eyes (10.0%) had glaucoma during a mean of 3.06±4.11 years of follow-up. The incidence of glaucoma was 6.9% (17/247) in stage 4A, 12.0% (16/133) in stage 4B, and 33.3% (7/21) in stage 5 ROP. Twenty-one percent of eyes (87/401) required lensectomy at a mean of 1.23±2.19 years after LSV. In univariate analysis, having stage 5 ROP (vs. stage 4 ROP) and presence of lensectomy were found to be significantly associated with time to glaucoma (hazard ratio = 6.76, 95% confidence interval = 2.19-20.88, P = 0.001; hazard ratio = 3.06, 95% confidence interval = 1.56-6.0, P = 0.001, respectively). In multivariate analysis, lensectomy was the only significant independent factor associated with time to glaucoma (hazard ratio = 2.76, 95% confidence interval = 1.371-5.581, P = 0.004).

Conclusions: Patients with more severe ROP had a higher incidence of glaucoma after lens-sparing vitrectomy. If a patient required lensectomy owing to progression of ROP and/or presence of lens opacity, then the hazard of having glaucoma significantly increased compared with those without lensectomy.
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http://dx.doi.org/10.1016/j.ophtha.2017.11.009DOI Listing
May 2018

Terson Syndrome Before Induction Chemotherapy for Acute Lymphoblastic Leukemia.

J Pediatr Hematol Oncol 2018 03;40(2):141-142

Departments of Pediatric Hematology-Oncology.

A previously healthy 2-year-old female infant presented with pancytopenia and was diagnosed with acute lymphoblastic leukemia. Before the initiation of treatment, she developed symptoms concerning for increased intracranial pressure. Head imaging revealed left parietal hemorrhage, in addition to a right vitreous hemorrhage, which was confirmed on ophthalmology examination later. Terson syndrome, in which intraocular hemorrhage is associated with intracranial hemorrhage, is more commonly reported in adults, although ocular manifestations of leukemia have been reported at presentation and are typically asymptomatic.
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http://dx.doi.org/10.1097/MPH.0000000000001047DOI Listing
March 2018

COMPARISON OF 3 MM × 3 MM VERSUS 6 MM × 6 MM OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY SCAN SIZES IN THE EVALUATION OF NON-PROLIFERATIVE DIABETIC RETINOPATHY.

Retina 2019 Feb;39(2):259-264

Shiley Eye Institute, University of California, San Diego, Department of Ophthalmology, La Jolla, California.

Purpose: To evaluate the utility of different optical coherence tomography angiography scan protocols in evaluating retinal changes in non-proliferative diabetic retinopathy.

Methods: Patients were imaged with the RTVue XR Avanti OCT 3 mm × 3 mm and 6 mm × 6 mm "Angio Retina" scan protocols. Ability to clearly delineate the foveal avascular zone (FAZ), FAZ remodeling, microaneurysms, capillary nonperfusion, motion, and doubling artifacts were evaluated.

Results: Forty-six eyes from 27 patients were enrolled. Eighty-nine percent of 3 mm × 3 mm versus 59% of 6 mm × 6 mm scans clearly delineated the FAZ (P = 0.001). Eighty percent of 3 mm × 3 mm versus 43% of 6 mm × 6 mm scans demonstrated FAZ remodeling (P = 0.0002). Microaneurysms were detected by 57% of 6 mm × 6 mm and 35% of 3 mm × 3 mm scans (P = 0.003). Capillary nonperfusion was detected in 87% of 3 mm × 3 mm scans versus 89% of 6 mm × 6 mm scans (P = 0.99). No significant differences were noted in the incidence of artifacts between the scan sizes (motion artifact P = 0.29 and doubling artifact P = 0.29).

Conclusion: 3 mm × 3 mm scan delineated FAZ and remodeling better than 6 mm × 6 mm scan, likely because of its higher scan density. 6 mm × 6 mm scans detected microaneurysms more readily than 3 mm × 3 mm, likely because of its larger scan area. There were utility for both 3 mm × 3 mm and 6 mm × 6 mm scans when evaluating these patients.
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http://dx.doi.org/10.1097/IAE.0000000000001951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963959PMC
February 2019

Identification of the genetic determinants responsible for retinal degeneration in families of Mexican descent.

Ophthalmic Genet 2018 Jan-Feb;39(1):73-79. Epub 2017 Sep 25.

d Shiley Eye Institute, University of California San Diego , La Jolla , CA , USA.

Purpose: To investigate the clinical characteristics and genetic basis of inherited retinal degeneration (IRD) in six unrelated pedigrees from Mexico.

Methods: A complete ophthalmic evaluation including measurement of visual acuities, Goldman kinetic or Humphrey dynamic perimetry, Amsler test, fundus photography, and color vision testing was performed. Family history and blood samples were collected from available family members. DNA from members of two pedigrees was examined for known mutations using the APEX ARRP genotyping microarray and one pedigree using the APEX LCA genotyping microarray. The remaining three pedigrees were analyzed using a custom-designed targeted capture array covering the exons of 233 known retinal degeneration genes. Sequencing was performed on Illumina HiSeq. Reads were mapped against hg19, and variants were annotated using GATK and filtered by exomeSuite. Segregation and ethnicity-matched control sample analyses were performed by dideoxy sequencing.

Results: Six pedigrees with IRD were analyzed. Nine rare or novel, potentially pathogenic variants segregating with the phenotype were detected in IMPDH1, USH2A, RPE65, ABCA4, and FAM161A genes. Among these, six were known mutations while the remaining three changes in USH2A, RPE65, and FAM161A genes have not been previously reported to be associated with IRD. Analysis of 100 ethnicity-matched controls did not detect the presence of these three novel variants indicating, these are rare variants in the Mexican population.

Conclusions: Screening patients diagnosed with IRD from Mexico identified six known mutations and three rare or novel potentially damaging variants in IMPDH1, USH2A, RPE65, ABCA4, and FAM161A genes that segregated with disease.
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http://dx.doi.org/10.1080/13816810.2017.1373830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143363PMC
March 2018

Handheld Optical Coherence Tomography Angiography and Ultra-Wide-Field Optical Coherence Tomography in Retinopathy of Prematurity.

JAMA Ophthalmol 2017 09;135(9):977-981

Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland.

Importance: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide. Optical coherence tomography (OCT) has improved the care of adults with vitreoretinal disease, and OCT angiography (OCTA) is demonstrating promise as a technique to visualize the retinal vasculature with lower risk and cost than fluorescein angiography. However, to date, there are no commercially available devices able to obtain ultra-wide-field OCT or OCTA images in neonates.

Objective: To obtain ultra-wide-field OCT and OCTA images in neonates with ROP using a prototype handheld OCT and OCTA device.

Design, Setting, And Participants: This observational case series was conducted from March 1 to April 1, 2017, in an academic medical center among 4 neonates with ROP in the neonatal intensive care unit and in the operating room.

Main Outcomes And Measures: Acquisition of wide-field OCT and OCTA images using a handheld prototype OCTA and ultra-wide-field OCT device.

Results: Images were obtained from 4 neonates (1 girl and 3 boys; mean age, 38 weeks' postmenstrual age [range, 34-43 weeks]) with various stages of ROP: 3 in the neonatal intensive care unit and 1 in the operating room. The system can obtain noncontact en face OCT images and horizontal line scans with an approximately 40° field of view and up to 100° (ultra-wide-field) using a contact lens-based approach in a single 2-second scan. In addition, 20° × 20° (approximately 4 × 4-mm) OCTA scans were obtained in patients with ROP in a single 2-second scan.

Conclusions And Relevance: Optical coherence tomography and OCTA are gaining popularity in pediatric retinal imaging. This study reports on OCTA and ultra-wide-field OCT images in 4 neonates with various stages of ROP that were obtained using a prototype handheld device. Additional studies will be needed to prove the clinical value of this technology.
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http://dx.doi.org/10.1001/jamaophthalmol.2017.2481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583755PMC
September 2017