Repeatability and reproducibility of quantitative OCT angiography measurements from table-top and portable Flex Spectralis devices.

PURPOSE: The recent development of a portable investigational handheld OCT-angiography (OCTA) device has allowed for expansion of imaging into the operating room (OR) in addition to standard in-clinic imaging. The aim of this study was to assess intravisit repeatability and intervisit reproducibility of retinal microvasculature measures and central retinal thickness for in-clinic table-top and portable OR compatible OCTA devices. METHODS: Repeated 10 × 10 OCTA images were acquired in 20 healthy adult participants on two separate visit days using Spectralis spectral-domain OCTA table-top and investigational armature suspended Flex systems. Intravisit and intervisit intraclass correlation coefficients and average absolute percent difference were calculated for quantitative microvasculature measures and CRT. RESULTS: 120 OCTA images were acquired from 20 subjects (n = 20, mean age 26.7 ± 1.61 years, range 24-30 years) with both devices across two separate imaging days. FAZ and CRT measurements had near complete intravisit and intervisit agreement with ICCs between .97 and 1 for both table-top (FAZ ICC .97, .97; CRT ICC .98-1, .98-.99) and Flex (FAZ ICC .97, .95; CRT ICC .99-1, .98-.99) devices. Vessel density measures demonstrated greater variance with only fair to strong agreement (ICC .32-.75) and average absolute percent differences ranging from 2.96 to 6.63%. CONCLUSION: FAZ and CRT measures for both devices demonstrated high repeatability and reproducibility; retinal vessel density measures demonstrated less. Differences of less than 7% for retinal microvasculature measurements across time and devices are most likely attributable to expectable variance between repeat scans.

Retinal Vasculitis and Intraocular Inflammation after Intravitreal Injection of Brolucizumab.

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.

Recent developments in pediatric retina.

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.

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

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.

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

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.

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

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.

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

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 mm2; 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 (R2 = 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 (R2 = 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.

VISUALIZATION FROM INTRAOPERATIVE SWEPT-SOURCE MICROSCOPE-INTEGRATED OPTICAL COHERENCE TOMOGRAPHY IN VITRECTOMY FOR COMPLICATIONS OF PROLIFERATIVE DIABETIC RETINOPATHY.

PURPOSE: To evaluate the use of live volumetric (4D) intraoperative swept-source microscope-integrated optical coherence tomography in vitrectomy for proliferative diabetic retinopathy complications. METHODS: In this prospective study, we analyzed a subgroup of patients with proliferative diabetic retinopathy complications who required vitrectomy and who were imaged by the research swept-source microscope-integrated optical coherence tomography system. In near real time, images were displayed in stereo heads-up display facilitating intraoperative surgeon feedback. Postoperative review included scoring image quality, identifying different diabetic retinopathy-associated pathologies and reviewing the intraoperatively documented surgeon feedback. RESULTS: Twenty eyes were included. Indications for vitrectomy were tractional retinal detachment (16 eyes), combined tractional-rhegmatogenous retinal detachment (2 eyes), and vitreous hemorrhage (2 eyes). Useful, good-quality 2D (B-scans) and 4D images were obtained in 16/20 eyes (80%). In these eyes, multiple diabetic retinopathy complications could be imaged. Swept-source microscope-integrated optical coherence tomography provided surgical guidance, e.g., in identifying dissection planes under fibrovascular membranes, and in determining residual membranes and traction that would benefit from additional peeling. In 4/20 eyes (20%), acceptable images were captured, but they were not useful due to high tractional retinal detachment elevation which was challenging for imaging. CONCLUSION: Swept-source microscope-integrated optical coherence tomography can provide important guidance during surgery for proliferative diabetic retinopathy complications through intraoperative identification of different complications and facilitation of intraoperative decision making.

Comparison of Visual Outcomes in Coats' Disease: A 20-Year Experience.

PURPOSE: To report differences in visual acuities among patients with Coats' disease who sought treatment at a tertiary care university-based practice. DESIGN: Single-center retrospective cohort study. PARTICIPANTS: Patients with Coats' disease diagnosed clinically, angiographically, or both from 1995 through 2015. METHODS: Patients were divided into 2 groups based on date of presentation: decade 1 (1995-2005) and decade 2 (2006-2015). MAIN OUTCOME MEASURES: Visual acuity (VA). RESULTS: Thirty-nine eyes of 39 patients were included with 19 eyes presenting in decade 1 and 20 eyes presenting in decade 2. Three patients demonstrated bilateral disease, but only the worse eye was included for analysis. Forty-seven percent of eyes in decade 1 demonstrated advanced stages of disease (stage 3B or worse) compared with 20% of eyes in decade 2. There was a trend for the mean initial presenting VA (±standard deviation) for decade 1 eyes to be worse (2.05±1.29 logarithm of the minimum angle of resolution [logMAR]) than for decade 2 eyes (1.45±0.99 logMAR; P = 0.1). From initial to final follow-up visit, mean VA also worsened for decade 1 eyes (P = 0.03), but remained stable for decade 2 eyes (P = 1.0). At the end of follow-up, there was a trend for mean VA for decade 1 eyes (2.28±1.17 logMAR) to be worse than for decade 2 eyes (1.60±1.15 logMAR; P = 0.07). Eight eyes were observed initially in decade 1 compared with 1 eye in decade 2, and only 1 of the observed eyes (in decade 2) developed painful glaucoma requiring enucleation. Decade 2 eyes had a higher average number of procedures per eye (6.5±4.9) compared with decade 1 eyes (1.4±1.7; P < 0.001). CONCLUSIONS: The earlier presentation of disease in decade 2 suggests improvements in disease detection over time. Furthermore, there was a trend for eyes to have better final VA in this decade. This is due to a combination of factors, including earlier presentation of disease, fewer eyes being observed without treatment, and eyes, when treated, receiving a higher number of procedures.

FUNCTIONAL OUTCOMES OF YOUNG INFANTS WITH AND WITHOUT MACULAR EDEMA.

PURPOSE: The authors relate posterior segment microanatomy from perinatal spectral domain optical coherence tomography to visual acuity, brain abnormalities, and neurodevelopment. METHODS: Thirteen infants (11 preterm and 2 term birth), imaged in the nursery with portable spectral domain optical coherence tomography, had visual acuity and sensorimotor testing at age 9 months to 15 months (grating acuity) or 4 years to 5 years (optotype), and medical records reviewed for brain magnetic resonance imaging reports and Bayley scales testing at age 18 months to 24 months. RESULTS: Eight children with age-appropriate macular microanatomy without edema on perinatal spectral domain optical coherence tomography had optimal (≥ 20/40) or within normal limits (grating acuity) visual acuity. Five children with perinatal macular edema had suboptimal visual acuity (in 9/10 eyes) and sensorimotor deficits, magnetic resonance imaging abnormalities, or poor neurodevelopment. Macular edema persisted in 1 infant through 9-month corrected age. CONCLUSION: Maturation of the visual system and evolution of retinal anomalies can be monitored with posterior segment spectral domain optical coherence tomography. Retinal microanatomy observed in infancy might relate to subsequent vision and other central nervous system events, but additional studies are needed to determine the range of normal microanatomy in infants and how this relates to vision and neurodevelopment.

Acute retinal pigment epithelium detachments after photocoagulation.

PURPOSE: To characterize the morphology of patterned scanning laser (PASCAL) panretinal photocoagulation. METHODS: In this prospective cohort study, patients with proliferative diabetic retinopathy or severe nonproliferative diabetic retinopathy with high-risk characteristics, who were treated with PASCAL panretinal photocoagulation as part of their indicated clinical course, were serially imaged with spectral domain optical coherence tomography. Thirty eyes of 25 patients were studied from 1 hour to 21 weeks after laser treatment. RESULTS: Over a quarter (26.1%) of all treatment spots were imaged by spectral domain optical coherence tomography 1 hour after PASCAL panretinal photocoagulation. At 1 hour (±30 minutes) after PASCAL treatment, spectral domain optical coherence tomography demonstrated retinal pigment epithelium detachment in 23 of 27 eyes (85.2%) and in 36.1% of all imaged laser spots. Detachments occurred preferentially at the photocoagulation edges in 48.4% of pigment epithelium detachments (PEDs). Linear regression analysis revealed that average laser power (Pearson's r = 0.671, P < 0.001) and average laser energy (Pearson's r = 0.588, P = 0.001) were significantly associated with PEDs observed 1 hour after treatment. Pigment epithelium detachments occurred at a rate of 9.2% ± 4.9% at an average power of 0 mW to 400 mW, 37.8% ± 9.5% at 401 mW to 800 mW, 42.1% ± 5.6% at 801 mW to 1,200 mW, and 53.6% ± 5.7% at >1,200 mW. By a 1-week follow-up, no PEDs were observed, and the retinal pigment epithelium appeared morphologically similar to its preoperative structure by 3 weeks. Patient characteristics (study eye, sex, race, diagnosis, age, preoperative blood glucose, hemoglobin A1C, duration of diabetes, and body mass index) and other PASCAL parameters (number of laser applications, spot size, pulse duration, and average laser fluence) were not significantly associated with PEDs. CONCLUSION: Retinal pigment epithelium detachment occurs 1 hour after PASCAL treatment over a wide range of laser settings. Laser power and energy are positively correlated with the occurrence of PEDs, which are no longer observed by 1-week follow-up. Future studies might examine various acute posttreatment time points and directly compare the morphology of PASCAL burns with that of longer pulse-duration laser modalities.

Vitamin D deficiency in neovascular versus nonneovascular age-related macular degeneration.

PURPOSE: To compare 25-hydroxyvitamin D (25OHD) levels in patients with neovascular age-related macular degeneration (NVAMD) with patients with nonneovascular age-related macular degeneration and control patients. METHODS: Medical records of all patients diagnosed with age-related macular degeneration and tested for serum 25OHD level at a single medical center were reviewed. Control patients were selected from patients diagnosed with pseudophakia but without age-related macular degeneration. The lowest 25OHD level available for each patient was recorded. RESULTS: Two hundred sixteen patients with nonneovascular age-related macular degeneration, 146 with NVAMD, and 100 non-age-related macular degeneration control patients were included. The levels of 25OHD (mean ± SD) were significantly lower in NVAMD patients (26.1 ± 14.4 ng/mL) versus nonneovascular age-related macular degeneration (31.5 ± 18.2 ng/mL, P = 0.003) and control (29.4 ± 10.1 ng/mL, P = 0.049) patients. The prevalence of vitamin D insufficiency (<30 ng/mL 25OHD), deficiency (<20 ng/mL), and severe deficiency (<10 ng/mL) were highest in the NVAMD group. The highest quintile of 25OHD was associated with a 0.35 (95% confidence interval, 0.18-0.68) odds ratio for NVAMD. CONCLUSION: This is the largest study to compare 25OHD levels in patients with the different clinical forms of age-related macular degeneration. Mean 25OHD levels were lower and vitamin D deficiency was more prevalent in NVAMD patients. These associations suggest that further research is necessary regarding vitamin D deficiency as a potentially modifiable risk factor for the development of NVAMD.

Transabdominal Fetal Ultrasound Before Early-Term Planned Delivery for Norrie Disease.

Purpose: To describe a case of early-term planned delivery of a fetus with Norrie disease. Methods: A retrospective chart review was performed. Results: A fetus with an older sibling with bilateral blindness from Norrie disease had positive NPD genetic testing on chorionic villus sampling. Transabdominal fetal ophthalmic ultrasound found bilateral total retinal detachments (RDs) at 32 weeks gestational age. The fetus was delivered at 37 weeks and had an examination under anesthesia, which showed bilateral inoperable RDs. Conclusions: Transabdominal fetal ophthalmic ultrasound was able to identity bilateral total RDs in utero. Further study is warranted on preterm or early-term delivery if a fetus has evidence of RD in utero.

Chronic Effects of e-Cigarette Aerosol Inhalation on Macular Perfusion Assessed Using OCT Angiography.

Purpose: To determine whether there are significant differences in the microvasculature and central retinal thickness (CRT) between e-cigarette users (user group) and age-matched nonusers (control group) using optical coherence tomography angiography (OCTA). Methods: In this prospective cross-sectional observational study, OCTA images were acquired of 52 eyes of 26 users and 25 eyes of 25 age-matched nonusers. Daily e-cigarette users with no ocular history were identified from provider information in the electronic medical record. A custom algorithm was used to calculate the foveal avascular zone (FAZ), vessel area density (VAD), and vessel length density (VLD). OCT software was used to calculate the foveal, superior, inferior, nasal, and temporal CRT. Generalized estimating equations using the Z-statistic were used to determine how the FAZ, VAD, VLD, and CRT parameters varied between groups and to assess the differential contribution of descriptive data in the user group. Results: No statistically significant difference was found between the user group and control group in the FAZ, superficial vascular complex (SVC) VAD, SVC VLD, or deep vascular complex (DVC) VAD. A statistically significant difference was found for DVC VLD (P = .002), with the user group having a slightly higher VLD on average. Superior, temporal, and inferior inner macular thicknesses were significantly thinner in the user group (P = .038, P = .012, and P = .035, respectively). Conclusions: Significant negative differences were found in CRT measures but not in retinal microvasculature parameters between e-cigarette users and nonusers. Decreased inferior, temporal, and superior inner macular thickness in e-cigarette users may show an early chronic structural effect that warrants further assessment of retinal effects as this population ages and continues to use e-cigarettes.

Intraoperative OCT-Guided Volumetric Measurements of Subretinal Therapy Delivery in Humans.

Purpose: To evaluate a recently developed technique using intraoperative optical coherence tomography (OCT) to measure subretinal tissue plasminogen activator (tPA) volumes in patients with submacular hemorrhage secondary to exudative age-related macular degeneration (AMD). Methods: Three patients (72 to 83 years old) had 25-gauge pars plana vitrectomy, subretinal tPA, and a partial gas fill. An investigational intraoperative OCT system with a modified widefield noncontact indirect viewing apparatus was used to image subretinal tPA blebs. Using the recently developed technique, the volume and surface area in the segmented region of interest were determined. Results: In each case, the delivered tPA volume measured from the syringe differed from the intraoperative OCT-measured subretinal tPA volume: Patient 1, 130 µL from syringe, 118 µL based on intraoperative OCT, 9% difference; Patient 2, 140 µL, 50 µL, 64%; Patient 3, 110 µL, 122 µL, 11%. The total bleb surface area was 129 mm2 in Patient 1, 55 mm2 in Patient 2, and 106 mm2 in Patient 3. Conclusions: This was the first human study to implement and evaluate intraoperative OCT image-based methods to obtain volumetric bleb measurements in patients receiving subretinal tPA for exudative AMD. This proof-of-concept study showed that intraoperative OCT-obtained bleb volume differed from intraoperative recordings, which could be explained by tPA delivery into the vitreous, efflux through the retinotomy, or human error. Intraoperative OCT can provide visualization and quantification of subretinal tPA bleb volume and surface area, which has implications for improved safety, efficacy, and analysis of the effects of subretinal drug delivery.

Longitudinal Choroidal Development in Preterm Infants.

Purpose: To characterize changes in subfoveal choroidal thickness in preterm infants from 30 to 60 weeks' postmenstrual age (PMA). Design: The prospective, observational Study of Eye Imaging in Preterm infantS (BabySTEPS) enrolled infants eligible for retinopathy of prematurity screening per the American Association of Pediatrics guidelines. Subjects: Infants imaged with an investigational, handheld OCT at ≥ 4 distinct imaging sessions between 30 to 60 weeks' PMA as part of BabySTEPS. Methods: Average choroidal thickness across the central subfoveal 1 mm in each eye at each time point was measured using custom segmentation software, and errors were manually corrected by a trained grader. We prospectively collected birth history data. A segmented mixed model was used to analyze the change in choroidal thickness as a function of PMA, birth weight, and gestational age (GA). Main Outcome Measures: Characterization of normative subfoveal choroidal thickness values and choroidal growth rate between 30 to 60 weeks' PMA. Results: We included 592 imaging sessions of 79 preterm infants (152 eyes). Mean (± standard deviation) GA was 27.5 ± 2.5 weeks. Mean choroidal thickness was 141.4 ± 34.5 µm at 30 weeks, 272.2 ± 83.9 µm at 38 weeks, and 306.2 ± 77.4 µm between 56 and 60 weeks. Between 30 and 60 weeks' PMA, choroidal growth followed a biphasic model, with a linear growth rate of 14.8 µm per week (95% confidence interval [CI], 13.6-16.0) from 30 until 38.4 weeks, then cessation of growth, with a growth rate of 0.3 µm per week (95% CI, -1.1 to 1.6) from 38.4 to 60 weeks. Infants with extremely low birth weight (ELBW; < 1000 g) and extremely preterm (GA < 28 weeks) infants had significantly slower initial growth rates compared with very low and low birth weight and very preterm and preterm infants (ELBW 13.0 vs. 21.0 µm per week; P < 0.0001 and extremely preterm 13.2 vs. 18.0 µm per week; P = 0.003). Conclusions: Preterm infant choroidal thickness experiences rapid linear growth from 30 to 38 weeks' PMA, at which time growth nearly stops. These foundational measurements and identification of the impact of extremes of low birth weight and prematurity on choroidal development will be essential as researchers begin to understand the role of choroidal development in ocular and retinal health in human infants. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Update on Retinal Drug Safety: Proceedings of the ASRS ReST Committee Webinar Part 1.

Purpose: To review the first Research and Safety in Therapeutics (ReST) Committee webinar and summarize the most current recommendations regarding diagnosis and management. Methods: The ReST Committee is comprised of members of the American Society of Retina Surgeons (ASRS). At regular internal meetings, safety issue reports from the website are reviewed. A webinar series was started in 2021 to update members on multiple relevant potential safety events. Results: Topics reviewed in the webinar included pentosan polysulfate sodium (Elmiron) maculopathy, intraocular pressure elevation reported with the aflibercept prefilled syringe (PFS), and brolucizumab-associated inflammation with occlusive retinal vasculitis. Retinal toxicity related to intraoperative medications was reviewed, including hemorrhagic occlusive retinal vasculitis after intraocular vancomycin, dilution errors with intravitreal aminoglycosides, inadvertent overdoses of cefuroxime after cataract surgery, and toxic posterior segment syndrome after dropless cataract surgery using compounded triamcinolone-moxifloxacin. Indocyanine green toxicity has been reported after its use as an adjuvant during macular hole surgery. Conclusions: The past decade has seen advances in retinal pharmaceuticals and drug-delivery devices. The ASRS ReST Committee collects data from its website reporting system to inform members about up-to-date pharmaceutical and device safety concerns. Recently, a webinar was used to inform members of pigmentary maculopathy associated with pentosan polysulfate sodium, safety regarding the aflibercept PFS, intraocular inflammation and occlusive retinal vasculitis secondary to brolucizumab, and retinal toxicity from intraoperative ocular medications.

Vision Loss Reduction with Avacincaptad Pegol for Geographic Atrophy: A 12-Month Post Hoc Analysis of the GATHER1 and GATHER2 Trials.

PURPOSE: To evaluate the impact of reduction in geographic atrophy (GA) lesion growth on visual acuity in the GATHER trials using categorical outcome measures. DESIGN: Randomized, double-masked, sham-controlled phase 3 trials. PARTICIPANTS: Aged ≥50 years with noncenter point-involving GA and best-corrected visual acuity (BCVA) of 25 to 80 ETDRS letters in the study eye. METHODS: GATHER1 consisted of 2 parts. In part 1, 77 patients were randomized 1:1:1 to avacincaptad pegol (ACP) 1 mg, ACP 2 mg, and sham. In part 2, 209 patients were randomized 1:2:2 to ACP 2 mg, ACP 4 mg, and sham. In GATHER2, patients were randomized 1:1 to ACP 2 mg (n = 225) and sham (n = 223). A post hoc analysis of 12-month data for pooled ACP 2 mg and sham groups is reported. MAIN OUTCOME MEASURES: Proportion of study eyes that experienced ≥10-, ≥15-, or ≥20-BCVA ETDRS letter loss from baseline to month 12; time-to-event analysis of persistent vision loss of ≥10, ≥15, or ≥20 BCVA letters from baseline at ≥2 consecutive visits over 12 months; proportion of study eyes with BCVA loss to a level below driving eligibility threshold at month 12 among those eligible to drive at baseline. RESULTS: Lower proportions of study eyes experienced ≥10-, ≥15-, or ≥20-BCVA letter loss from baseline over 12 months with ACP 2 mg (11.6%, 4.0%, and 1.6%, respectively) versus sham (14.1%, 7.6%, and 4.5%, respectively). There was a reduction in the risk of persistent loss of ≥15 BCVA ETDRS letters with ACP 2 mg (3.4%) versus sham (7.8%) through 12 months. A lower proportion of study eyes treated with ACP 2 mg reached the threshold for driving ineligibility versus sham by 12 months. CONCLUSIONS: Treatment with ACP 2 mg delayed the risk of progression to persistent vision loss (i.e., ≥10-, ≥15-, and ≥20-BCVA letter loss or BCVA loss to a level below driving eligibility threshold) versus sham over 12 months. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Fluocinolone Acetonide Implant Removal From the Vitreous Cavity.

Purpose: To describe a technique for fluocinolone acetonide implant removal from the vitreous cavity. Methods: A case report and review of surgical methods were performed. Results: The technique to remove a fluocinolone acetonide implant from the vitreous cavity was safe and effective. The vitreous cutter was used to align the implant coaxially with a 25-gauge cannula. The valve of the cannula was opened, creating pressure that drew the implant into the cannula. Conclusions: Fluocinolone acetonide implants can be efficiently removed from the vitreous cavity by creating a pressure differential using the valved cannula. Advantages of this technique include avoiding invasive maneuvers such as enlarging the sclerotomy or creating a corneal wound.