Vital Dyes in Vitreomacular Surgery

Vital dyes contain complex molecules with chromophores that stain living tissues and have greatly enhanced identification and removal of transparent vitreoretinal tissues during surgery. Several “chromovitrectomy” dyes are frequently used by vitreoretinal specialists, including indocyanine green, trypan blue, brilliant blue G, and triamcinolone acetonide; other dyes are also under investigation. Trypan Blue was approved by the U.S. Food and Drug Administration (FDA) for epiretinal membrane removal, and preservative-free triamcinolone acetonide was approved by the FDA for intraocular use. However, currently available chromovitrectomy dyes have their limitations, and of particular concern for some of them is the possibility for acute and chronic toxicity to the neurosensory retina and retinal pigmented epithelium. The potentially irreversible acute toxicity and other limitations, such as lack of long-term safety profiles, highlight the need for further advancements

En Face Enhanced-Depth Swept-Source Optical Coherence Tomography Features of Chronic Central Serous Chorioretinopathy

Objective To characterize en face features of the retinal pigment epithelium (RPE) and choroid in eyes with chronic central serous chorioretinopathy (CSCR) using a high-speed, enhanced-depth swept-source optical coherence tomography (SS-OCT) prototype. Design Consecutive patients with chronic CSCR were prospectively examined with SS-OCT. Participants Fifteen eyes of 13 patients. Methods Three-dimensional 6×6 mm macular cube raster scans were obtained with SS-OCT operating at 1050 nm wavelength and 100 000 A-lines/sec with 6 μm axial resolution. Segmentation of the RPE generated a reference surface; en face SS-OCT images of the RPE and choroid were extracted at varying depths every 3.5 μm (1 pixel). Abnormal features were characterized by systematic analysis of multimodal fundus imaging, including color photographs, fundus autofluorescence, fluorescein angiography, and indocyanine-green angiography (ICGA). Main Outcome Measures En face SS-OCT morphology of the RPE and individual choroidal layers. Results En face SS-OCT imaging at the RPE level revealed absence of signal corresponding to RPE detachment or RPE loss in 15 of 15 (100%) eyes. En face SS-OCT imaging at the choriocapillaris level showed focally enlarged vessels in 8 of 15 eyes (53%). At the level of Sattler's layer, en face SS-OCT documented focal choroidal dilation in 8 of 15 eyes (53%) and diffuse choroidal dilation in 7 of 15 eyes (47%). At the level of Haller's layer, these same features were observed in 3 of 15 eyes (20%) and 12 of 15 eyes (80%), respectively. In all affected eyes, these choroidal vascular abnormalities were seen just below areas of RPE abnormalities. In 2 eyes with secondary choroidal neovascularization (CNV), distinct en face SS-OCT features corresponded to the neovascular lesions. Conclusions High-speed, enhanced-depth SS-OCT at 1050 nm wavelength enables the visualization of pathologic features of the RPE and choroid in eyes with chronic CSCR not usually appreciated with standard spectral domain (SD) OCT. En face SS-OCT imaging seems to be a useful tool in the identification of CNV without the use of angiography. This in vivo documentation of the RPE and choroidal vasculature at variable depths may help elucidate the pathophysiology of disease and can contribute to the diagnosis and management of chronic CSCR.National Institutes of Health (U.S.) (R01-EY011289-27)National Institutes of Health (U.S.) (R01-EY013178-12)National Institutes of Health (U.S.) (R01-EY018184-05)National Institutes of Health (U.S.) (R44EY022864-01)National Institutes of Health (U.S.) (GR01-CA075289-16)National Institutes of Health (U.S.) (R01-NS057476-05)National Institutes of Health (U.S.) (R44-EY022864-01)United States. Air Force Office of Scientific Research (FA9550-10-1-0551)United States. Air Force Office of Scientific Research (FA9550-10-1-0063)Research to Prevent Blindness, Inc. (United States)Massachusetts Lions ClubGerman Science Foundation (DFG-GSC80-SAOT

Characterizing New-Onset Exudation in the Randomized Phase 2 FILLY Trial of Complement Inhibitor Pegcetacoplan for Geographic Atrophy.

To evaluate clinical characteristics of eyes in which investigator-determined new-onset exudative age-related macular degeneration (eAMD) developed during the FILLY trial.Post hoc analysis of the phase 2 study of intravitreal pegcetacoplan in geographic atrophy (GA).Patients with GA secondary to age-related macular degeneration (AMD), n = 246.Either 15 mg intravitreal pegcetacoplan or sham given monthly or every other month for 12 months followed by a 6-month off-treatment period.Time of new eAMD onset in the study eye, history of eAMD in the fellow eye, presence of double-layer sign (DLS) on structural OCT in the study eye, changes in retinal anatomic features by structural OCT and fluorescein angiography (FA), and changes in visual acuity.Exudation was reported in 26 study eyes across treatment groups over 18 months. Mean time to eAMD diagnosis was 256 days (range, 31-555 days). Overall, a higher proportion of patients with a baseline history of eAMD in the fellow eye (P = 0.016) and a DLS in the study eye (P = 0.0001) demonstrated eAMD. Among study eyes in which eAMD developed, 18 of 26 (69%) had history of fellow-eye eAMD and 19 of 26 (73.1%) had DLS at baseline, compared with 76 of 217 study eyes (35%; P = 0.0007) and 70 of 215 study eyes (32.5%; P0.0001), respectively, in which eAMD did not develop. All 21 patients with structural OCT imaging at the time of eAMD diagnosis demonstrated subretinal fluid, intraretinal cysts, or both consistent with exudation. Among 17 patients who underwent FA at eAMD diagnosis, 10 showed detectable macular neovascularization (MNV), all occult lesions. Development of eAMD did not have an appreciable impact on visual acuity, and all patients responded to anti-vascular endothelial growth factor (VEGF) therapy.Intravitreal pegcetacoplan slowed the rate of GA growth and was associated with an unexpected dose-dependent increased incidence of eAMD with no temporal clustering of onset. Exudative AMD seemed to be associated with baseline eAMD in the contralateral eye and a DLS, suggestive of nonexudative MNV, in the study eye. The safety profile of pegcetacoplan was acceptable to proceed to phase 3 studies without adjustments to enrollment criteria

Characterization of Choroidal Layers in Normal Aging Eyes Using Enface Swept-Source Optical Coherence Tomography

Purpose To characterize qualitative and quantitative features of the choroid in normal eyes using enface swept-source optical coherence tomography (SS-OCT). Methods Fifty-two eyes of 26 consecutive normal subjects were prospectively recruited to obtain multiple three-dimensional 12x12mm volumetric scans using a long-wavelength high-speed SS-OCT prototype. A motion-correction algorithm merged multiple SS-OCT volumes to improve signal. Retinal pigment epithelium (RPE) was segmented as the reference and enface images were extracted at varying depths every 4.13 mu m intervals. Systematic analysis of the choroid at different depths was performed to qualitatively assess the morphology of the choroid and quantify the absolute thicknesses as well as the relative thicknesses of the choroidal vascular layers including the choroidal microvasculature (choriocapillaris, terminal arterioles and venules;CC) and choroidal vessels (CV) with respect to the subfoveal total choroidal thickness (TC). Subjects were divided into two age groups: younger (= 40 years). Results Mean age of subjects was 41.92 (24-66) years. Enface images at the level of the RPE, CC, CV, and choroidal-scleral interface were used to assess specific qualitative features. In the younger age group, the mean absolute thicknesses were: TC 379.4 mu m (SD +/- 75.7 mu m),CC 81.3 mu m (SD +/- 21.2 mu m) and CV 298.1 mu m (SD +/- 63.7 mu m). In the older group, the mean absolute thicknesses were: TC 305.0 mu m (SD +/- 50.9 mu m),CC 56.4 mu m (SD +/- 12.1 mu m) and CV 248.6 mu m (SD +/- 49.7 mu m). In the younger group, the relative thicknesses of the individual choroidal layers were: CC 21.5% (SD +/- 4.0%) and CV 78.4% (SD +/- 4.0%). In the older group, the relative thicknesses were: CC 18.9% (SD +/- 4.5%) and CV 81.1% (SD +/- 4.5%). The absolute thicknesses were smaller in the older age group for all choroidal layers (TC p=0.006, CC p=0.0003, CV p=0.03) while the relative thickness was smaller only for the CC (p=0.04). Conclusions Enface SS-OCT at 1050nm enables a precise qualitative and quantitative characterization of the individual choroidal layers in normal eyes. Only the CC is relatively thinner in the older eyes. In-vivo evaluation of the choroid at variable depths may be potentially valuable in understanding the natural history of age-related posterior segment disease

Avascular Peripheral Retina in Infants

Avascular peripheral retina in an infant is a common characteristic of numerous pediatric retinal vascular disorders and often presents a diagnostic challenge to the clinician. In this review, key features of each disease in the differential diagnosis, from retinopathy of prematurity, familial exudative vitreoretinopathy, Coats disease, incontinentia pigmenti, Norrie disease, and persistent fetal vasculature, to other rare hematologic conditions and telomere disorders, will be discussed by expert ophthalmologists in the field

Ophthalmology

PURPOSE: To evaluate the 2-year efficacy, durability, and safety of dual angiopoietin-2/vascular endothelial growth factor (VEGF)-A pathway inhibition with intravitreal faricimab according to a personalized treat-and-extend-based regimen (T&E) with up to every-16-week (Q16W) dosing in the YOSEMITE/RHINE (NCT03622580/NCT03622593) phase 3 trials of diabetic macular edema (DME). DESIGN: Randomized, double-masked, noninferiority phase 3 trials. PARTICIPANTS: Adults with visual acuity loss due to center-involving DME. METHODS: Patients were randomized 1:1:1 to faricimab 6.0 mg Q8W, faricimab 6.0 mg T&E (previously referred to as personalized treatment interval), or aflibercept 2.0 mg Q8W. The T&E up to Q16W dosing regimen was based on central subfield thickness (CST) and best-corrected visual acuity (BCVA) change. MAIN OUTCOME MEASURES: Included changes from baseline in BCVA and CST, number of injections, durability, absence of fluid, and safety through week 100. RESULTS: In YOSEMITE/RHINE (N=940/951), noninferior year 1 visual acuity gains were maintained through year 2; mean BCVA change from baseline at 2 years (weeks 92/96/100 average) with faricimab Q8W (YOSEMITE/RHINE, +10.7/+10.9 letters) or T&E (+10.7/+10.1 letters) were comparable with aflibercept Q8W (+11.4/+9.4 letters). The median number of study drug injections was lower with faricimab T&E (YOSEMITE/RHINE, 10/11 injections) versus faricimab Q8W (15 injections) and aflibercept Q8W (14 injections) across both trials during the entire study. In the faricimab T&E arms, durability was further improved during year 2, with >60% of patients on Q16W dosing and ∼80% on ≥Q12W dosing at week 96. Almost 80% of patients who achieved Q16W dosing at week 52 maintained Q16W dosing without an interval reduction through week 96. Mean CST reductions were greater, and more patients achieved absence of DME (CST <325μm) and absence of intraretinal fluid with faricimab Q8W or T&E versus aflibercept Q8W through year 2. Overall, faricimab was well tolerated, with a safety profile comparable to aflibercept. CONCLUSIONS: Clinically meaningful visual acuity gains from baseline, anatomic improvements, and extended durability with intravitreal faricimab up to Q16W were maintained through year 2. Faricimab given as a personalized T&E-based dosing regimen supports the role of dual angiopoietin-2/VEGF-A inhibition to promote vascular stability and provide durable efficacy for patients with DME

Self-Induced Laser Maculopathy in an Adolescent Boy Utilizing a Mirror

Laser maculopathy is a rare complication that can occur when a beam of laser light is focused directly on the macula. This report describes the first published case of self-induced laser pointer maculopathy that was secondary to laser beam reflection from a mirror. The patient demonstrated both visual and anatomic recovery during the follow-up period. In addition, the issue of discrepancy between the labeled and actual power of laser pointers is addressed