Retinal Nerve Fibre Layer Thickness Increases with Decreasing Spectralis OCT Signal Strength in Normal Eyes.

We sought to determine effect of signal strength on mean retinal nerve fibre layer (RNFL) using Spectralis optical coherence tomography (S-OCT). Thirty normal subjects (18 female, mean 37.9 years, range 24-61) were imaged with S-OCT using variably dense Bangerter foils to alter Q value (1 unit signal strength = 4 units Q). We found a statistically significant (p < 0.01) linear relationship (R = 0.8643) between Q and RNFL (1 unit decrease Q = 0.181 um mean RNFL increase). Unlike previous observations of Cirrus and Stratus OCT, we found RNFL thickness does not decrease with decreasing signal strength in S-OCT.

CELLULAR IMAGING OF THE TAPETAL-LIKE REFLEX IN CARRIERS OF RPGR-ASSOCIATED RETINOPATHY.

PURPOSE: To examine the features of the tapetal-like reflex (TLR) in female carriers of RPGR-associated retinopathy by means of adaptive optics scanning light ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography. METHODS: Nine molecularly confirmed RPGR carriers and three healthy controls underwent ocular examination and the following retinal imaging modalities: color photography, near-infrared reflectance, fundus autofluorescence, spectral domain optical coherence tomography, and AOSLO. After identifying TLR areas across all imaging modalities, normalized local contrast of outer retinal bands on spectral domain optical coherence tomography was calculated and AOSLO-acquired photoreceptor mosaic analysis was performed. RESULTS: Seven carriers had TLR areas, which colocalized with increased rod photoreceptor reflectivity on confocal AOSLO and reduced cone photoreceptor densities. Parafoveal TLR areas also exhibited reduced local contrast (i.e., increased reflectivity) of the outer retinal bands on spectral domain optical coherence tomography (inner segment ellipsoid zone and outer segment interdigitation zone). Healthy controls did not show TLR. CONCLUSION: The cellular resolution provided by AOSLO affords the characterization of the photoreceptor mosaic in RPGR carriers with a TLR. Features revealed include reduced cone density, increased cone inner segment diameter, and increased rod outer segment reflectivity.

Foveal Development in Infants Treated with Bevacizumab or Laser Photocoagulation for Retinopathy of Prematurity.

PURPOSE: To characterize and quantify early foveal development in preterm infants and to compare this development between eyes treated with intravitreal bevacizumab or laser photocoagulation (LPC) and untreated eyes. DESIGN: Observational case series. PARTICIPANTS: One hundred thirty-one preterm infants undergoing retinopathy of prematurity (ROP) screenings. METHODS: Handheld OCT imaging was performed longitudinally on all patients. Thickness measurements of the inner and outer retinal layers were obtained at the foveal center and the nasal and temporal foveal rims. Comparisons between treated and untreated eyes were adjusted for age and other confounding variables. MAIN OUTCOME MEASURES: Weekly change in inner and outer retinal thickness and presence of inner retinal layers, ellipsoid zone (EZ), and cystoid macular changes (CMCs). RESULTS: Outer retinal thickness at the foveal center increased by 3.1 µm/week in untreated eyes and 7.2 µm/week in bevacizumab-treated eyes (P = 0.038). Eyes treated with LPC had a lower probability of having all inner retinal layers present at the foveal center (odds ratio, 0.04; P = 0.001) and a lower probability of having the EZ present at the foveal center (odds ratio, 0.07; P = 0.024) compared with untreated eyes. Cystoid macular changes were found in 53% of patients and 22% of imaging sessions. The age-adjusted incidence of CMCs was not correlated with bevacizumab or LPC treatment. CONCLUSIONS: Intravitreal bevacizumab therapy for ROP is associated with more rapid outer retinal thickening at the foveal center, whereas LPC is associated with earlier extrusion of the inner retinal layers and delayed development of the EZ at the foveal center. Long-term follow-up is needed to determine the visual significance of these findings.

Retrospective Optimization of the Hawkeye Orbital Fracture Prioritization and Evaluation Algorithms for Triaging Ophthalmic Care.

Objectives: Many orbital fracture patients are transferred to tertiary care centers for immediate ophthalmology consultation, though few require urgent ophthalmic evaluation or intervention. This overutilizes limited resources and overburdens patients and the health care system with travel and emergency department (ED) expenses. A simple, easy-to-use, clinical decision-making tool is needed to aid local EDs and triage services in effectively identifying orbital fracture patients who need urgent ophthalmic evaluation. Design: Single center, retrospective cohort study. Subjects: Orbital fracture patients aged ≥ 18 years who presented to the study institution's emergency department and received an ophthalmology consultation. Methods: Ocular injuries that required close monitoring or an intervention within the first few hours after presentation were termed urgent. Two Hawkeye Orbital Fracture Prioritization and Evaluation (HOPE) algorithms were developed to identify orbital fracture patients needing urgent evaluation; including 1 algorithm incorporating computerized tomography (CT) scans interpreted by ophthalmology (HOPE+CT). Algorithms were compared with 3 previously published protocols: the University of Texas Health Science Center at Houston (UTH), the South Texas Orbital Fracture Protocol (STOP), and Massachusetts Eye and Ear (MEE) algorithms. Main Outcome Measures: Correct triage of patients with orbital fractures who have urgent ocular or orbital conditions. Results: In the study institution's ED, 134 adult patients (145 orbits) were seen with orbital fractures in 2019. Eighteen (13.4%) had ocular or orbital conditions categorized as urgent. The HOPE tool resulted in 100% sensitivity and 78.4% specificity. The HOPE+CT tool resulted in 100.0% sensitivity and 94.0% specificity. The UTH algorithm was 91.7% sensitive and 76.5% specific. South Texas Orbital Fracture Protocol and MEE were both 100% sensitive but only 35.1% and 32.8% specific, respectively. Conclusions: The HOPE and HOPE+CT algorithms were superior or equal to the UTH, STOP, and MEE algorithms in terms of specificity while detecting all urgent cases. Implementation of a triage protocol that uses the HOPE or HOPE+CT algorithms could improve resource utilization and reduce health care costs through identification of orbital fracture patients needing urgent evaluation. An online tool that deploys the HOPE+CT algorithm in a user-friendly interface has been developed and is undergoing prospective validation before public dissemination. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Xp11.3 microdeletion causing Norrie disease and X-linked Kabuki syndrome.

Purpose: To describe a novel case of Norrie disease and X-linked Kabuki syndrome caused by a microdeletion encompassing multiple genes on the X chromosome. Observations: A 3-day-old boy born at full term had bilateral retrolental fibrovascular plaques. Surgery with lensectomy and vitrectomy revealed bilateral, closed funnel retinal detachments consistent with a clinical diagnosis of Norrie disease. In addition, the baby had congenital heart defects, hearing loss, and dysmorphic facies. His mother carried a clinical diagnosis of Kabuki syndrome. Genetic testing of the baby revealed an Xp11.3 microdeletion that included the NDP and KDM6A genes, confirming the baby had both Norrie disease and X-linked Kabuki syndrome. The mother was found via ultrawide-field fluorescein angiography to have asymptomatic peripheral retinal vascular anomalies, consistent with NDP-associated familial exudative vitreoretinopathy (FEVR). Conclusions and importance: This is the first reported case of Norrie disease together with X-linked Kabuki syndrome. Contiguous gene deletions may explain some of the variable systemic involvement in Norrie disease.

Inpatient Adherence to Topical Glaucoma Medications before and after an Educational Intervention.

PURPOSE: To assess the inpatient adherence rate and factors associated with adherence to topical glaucoma medications (TGMs) at a single academic institution throughout hospitalization before and after an educational intervention. DESIGN: Nonrandomized, comparative, retrospective study. PARTICIPANTS: Inpatients 18 years of age and older admitted to a single academic hospital from January 2014 through June 2019 with a diagnosis of glaucoma who also received TGMs. METHODS: The medication administration record during admission was examined closely to determine if the TGMs were reconciled and administered correctly before and after an educational intervention with inpatient providers. A simple intervention reached various health care providers through an educational e-mail, communication in a weekly newsletter, and a morning report presentation. Adherence was defined as administration of more than 75% of recommended doses during the inpatient stay. Other collected variables included length of stay and primary diagnosis on admission. MAIN OUTCOME MEASURES: Adherence rate to inpatient administration of TGMs. RESULTS: One hundred eighty-four patients (n = 142 before intervention; n = 42 after intervention) were included. The preintervention group had a total of 275 TGMs, of which 207 (75.3%) were administered in accordance with the adherence definition of this study. After the intervention phase, 49 of 56 (87.5%) TGMs were administered with appropriate adherence (P = 0.047). Adherence was associated significantly with a known outpatient medication regimen (P = 0.006) and correct admission reconciliation (P < 0.001). CONCLUSIONS: When glaucoma patients requiring topical treatment are admitted, approximately one quarter of patients seem to not receive their medications appropriately. In this study, a simple educational intervention was able to improve adherence. To prevent daily fluctuations in intraocular pressure for vulnerable glaucoma patients, inpatient adherence to appropriate medication administration should be stressed continuously. While in the care of health care providers, inpatients should be afforded at least the opportunity to maintain adequate adherence, just as is carried out for other medications related to other chronic medical conditions.

INTRAOPERATIVE IMAGING OF RETAINED PERFLUOROCARBON LIQUID USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To report images of retained perfluorocarbon liquid (PFCL) on the surface of the retina obtained during an intraoperative use of hand-held spectral domain optical coherence tomography. METHODS: A 54-year-old man underwent pars plana vitrectomy with injection of PFCL to repair retinal detachment. Postoperatively, visually significant PFCL droplets were found to be retained in the eye. During the surgical removal of PFCL, a hand-held spectral domain optical coherence tomography was used to image the retina with the patient supine. RESULTS: Spectral domain optical coherence tomography images of the retained PFCL illustrated magnification of the areas of the outer retina underlying PFCL bubbles. The images obtained had some similarities to the patient's own observation of "floaters." CONCLUSION: Droplets of PFCL over the retina result in imaging artifact, most likely due to a lensing effect caused by differences in refractive index between the PFCL and vitreous humor. Although the utility of hand-held spectral domain optical coherence tomography for infants has previously been established, this case presents further application of spectral domain optical coherence tomography in adults when imaging in the supine position is required.

The Utility of Frame Averaging for Automated Algorithms in Analyzing Retinal Vascular Biomarkers in AngioVue OCTA.

PURPOSE: This study proposes an optical coherence tomography angiography (OCTA) frame-averaging method and investigates the effects of the number of frames acquired and averaged on metrics quantifying the foveal avascular zone (FAZ), vessel morphology, and parafoveal intercapillary area (PICA). METHODS: Ten OCTA frames were acquired for each of the 19 subjects without known retinal disease using the AngioVue OCTA system. For each subject, acquired frames were ranked by an image quality metric. A subset of frames was then registered and averaged. The effects of the number of frames acquired and averaged on FAZ segmentation and metrics of FAZ geometry, vessel morphology, and PICA were analyzed. RESULTS: Frame averaging increased the accuracy of the automatically segmented FAZ region; for example, the absolute error in FAZ area decreased from 0.026 mm2 (1 frame) to 0.005 mm2 (5 frames). Averaging multiple frames exponentially decreased the estimated number of vessel endpoints and increased the average vessel length with a 32% decrease in number of endpoints and 14% increase in average vessel length when averaging five frames compared with one. Frame averaging also improved the precision of PICA estimates. CONCLUSIONS: Averaging multiple OCTA frames using the Optovue AngioVue system reduced error in FAZ segmentation and improved the robustness of OCTA vessel morphology and perfusion metrics. The study demonstrated limited benefit in acquiring and averaging more than five frames. TRANSLATIONAL RELEVANCE: Averaging multiple OCTA frames improved the robustness of OCTA foveal biomarkers with limited benefit when averaging more than five frames.

Assessing the Interocular Symmetry of Foveal Outer Nuclear Layer Thickness in Achromatopsia.

PURPOSE: We examine the interocular symmetry of foveal outer nuclear layer (ONL) thickness measurements in subjects with achromatopsia (ACHM). METHODS: Images from 76 subjects with CNGA3- or CNGB3-associated ACHM and 42 control subjects were included in the study. Line or volume scans through the fovea of each eye were acquired using optical coherence tomography (OCT). Image quality was assessed for each image included in the analysis using a previously-described maximum tissue contrast index (mTCI) metric. Three foveal ONL thickness measurements were made by a single observer and interocular symmetry was assessed using the average of the three measurements for each eye. RESULTS: Mean (± standard deviation) foveal ONL thickness for subjects with ACHM was 79.7 ± 18.3 µm (right eye) and 79.2 ± 18.7 µm (left eye) compared to 112.9 ± 15.2 (right eye) and 112.1 ± 13.9 µm (left eye) for controls. Foveal ONL thickness did not differ between eyes for ACHM (P = 0.636) or control subjects (P = 0.434). No significant relationship between mTCI and observer repeatability was observed for either control (P = 0.140) or ACHM (P = 0.351) images. CONCLUSIONS: While foveal ONL thickness is reduced in ACHM compared to controls, the high interocular symmetry indicates that contralateral ONL measurements could be used as a negative control in early-phase monocular treatment trials. TRANSLATIONAL RELEVANCE: Foveal ONL thickness can be measured using OCT images over a wide range of image quality. The interocular symmetry of foveal ONL thickness in ACHM and control populations supports the use of the non-study eye as a control for clinical trial purposes.

Intraobserver Repeatability and Interobserver Reproducibility of Ellipsoid Zone Measurements in Retinitis Pigmentosa.

PURPOSE: To examine repeatability and reproducibility of ellipsoid zone (EZ) width measurements in patients with retinitis pigmentosa (RP) using a longitudinal reflectivity profile (LRP) analysis. METHODS: We examined Bioptigen optical coherence tomography (OCT) scans from 48 subjects with RP or Usher syndrome. Nominal scan lengths were 6, 7, or 10 mm, and the lateral scale of each scan was calculated using axial length measurements. LRPs were generated from OCT line scans, and the peak corresponding to EZ was manually identified using ImageJ. The locations at which the EZ peak disappeared were used to calculate EZ width. Each scan was analyzed twice by each of two observers, who were masked to their previous measurements and those of the other observer. RESULTS: On average, horizontal width (HW) was significantly greater than vertical width (VW), and there was high interocular symmetry for both HW and VW. We observed excellent intraobserver repeatability with intraclass correlation coefficients (ICCs) ranging from 0.996 to 0.998 for HW and VW measurements. Interobserver reproducibility was also excellent for both HW (ICC = 0.989; 95% confidence interval [CI] = 0.983-0.995) and VW (ICC = 0.991; 95% CI = 0.985-0.996), with no significant bias observed between observers. CONCLUSIONS: EZ width can be measured using LRPs with excellent repeatability and reproducibility. Our observation of greater HW than VW is consistent with previous observations in RP, though the reason for this anisotropy remains unclear. TRANSLATIONAL RELEVANCE: We describe repeatability and reproducibility of a method for measuring EZ width in patients with RP or Usher syndrome. This approach could facilitate measurement of retinal band thickness and/or intensity.

A case of congenital retinal macrovessel in an otherwise normal eye.

PURPOSE: To present the case of a 37-year-old female with a foveal macrovessel. OBSERVATIONS: The patient had an incidental finding of congenital retinal macrovessel (CRM) in the left eye on optical coherence tomography (OCT). Visual acuity was normal, and slit lamp and dilated fundus examinations were otherwise unremarkable. OCT angiography (OCTA) imaging allowed for visualization of the depth profile of the vessel as well as the foveal avascular zone (FAZ). The FAZ and foveal pit were both smaller in the affected eye compared to the fellow eye. CONCLUSIONS AND IMPORTANCE: We describe findings of OCTA imaging in a patient with CRM. Previous reports have relied on examination using fluorescein angiography, which does not provide sufficient axial resolution to discern the different vascular plexuses. This report further characterizes how this rare condition can affect foveal morphology and retinal vasculature.

Assessing the Accuracy of Foveal Avascular Zone Measurements Using Optical Coherence Tomography Angiography: Segmentation and Scaling.

PURPOSE: The foveal avascular zone (FAZ) is altered in numerous diseases. We assessed factors (axial length, segmentation method, age, sex) impacting FAZ measurements from optical coherence tomography (OCT) angiography images. METHODS: We recruited 116 Caucasian subjects without ocular disease, and acquired two 3 × 3 mm AngioVue scans per each right eye (232 total scans). In images of the superficial plexus, the FAZ was segmented using the AngioVue semiautomatic nonflow measurement tool and ImageJ manual segmentation. In images from the full retinal thickness, the FAZ was segmented using the AngioAnalytics automatic FAZ tool. Repeatability, reliability, and reproducibility were calculated for FAZ measurements (acircularity, area). RESULTS: FAZ area (mean ± SD) for manual segmentation was 0.240 ± 0.0965 mm2, greater than both semiautomatic (0.216 ± 0.0873 mm2) and automatic (0.218 ± 0.0869 mm2) segmentation (P < 0.05). Not correcting for axial length introduced errors up to 25% in FAZ area. Manual area segmentation had better repeatability (0.020 mm2) than semiautomatic (0.043 mm2) or automatic (0.056 mm2). FAZ acircularity had better repeatability with automatic than manual segmentation (0.086 vs. 0.114). Reliability of all area measurements was excellent (intraclass correlation coefficient [ICC] = 0.994 manual, 0.969 semiautomatic, 0.948 automatic). Reliability of acircularity measurements was 0.879 for manual and 0.606 for automatic. CONCLUSION: We identified numerous factors affecting FAZ measurements. These errors confound comparisons across studies and studies examining factors that may correlate with FAZ measures. TRANSLATIONAL RELEVANCE: Using FAZ measurements as biomarkers for disease progression requires assessing and controlling for different sources of error. Not correcting for ocular magnification can result in significant inaccuracy in FAZ measurements, while choice of segmentation method affects both repeatability and accuracy.