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Purpose: To identify and describe adverse events (AEs) observed with real-world use of the following 3 vitrectomy platforms: Constellation (Alcon), Enhancing Visual Acuity (EVA, Dutch Ophthalmic Research Center), and Stellaris (Bausch + Lomb). Methods: All reports submitted to the US Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database between January 2010 and November 2021 that were associated with the 3 vitrectomy platforms were analyzed. Each report was reviewed for AEs or consequences and the type of complication noted. Duplicates and reports with an inadequate narrative to categorize the event were excluded. A descriptive analysis was performed for the prevalence of device-specific issues within each platform. Results: The analysis included 2534 reports (1738 Constellation, 117 EVA, 679 Stellaris). Overall, the most commonly reported complications involved the vitrectomy probe (n = 957 [37.8%]) and the central processing unit (n = 368 [14.5%]). Differences in the distribution of AEs among the platforms were noted, with vitrectomy probe issues being the most reported events for the Constellation and Stellaris and infusion issues for the EVA. Infusion issues most frequently led to reports of patient harm with the Constellation (31/1738 [1.8%]) and EVA (7/116 [6.0%]), while issues with the vitrectomy probe were reported with the Stellaris (11/679 [1.6%]). Conclusions: An analysis of real-world data in the MAUDE database highlighted the spectrum of device-specific AEs of greatest relevance to surgical practice. Familiarity with potential device complications will help minimize harm to patients., Competing Interests: Dr. Kovas: Intergalactic Therapeutics (consultant). Dr. D’Amico: Alcon, Iveric Bio, and Aufbau Holdings (consultant); Iveric Bio and Aufbau Holdings (equity); Aufbau Holdings (intellectual property). Dr. Van Tassel: Alcon, Adverum, Abbvie, Equinox, New World Medical, Glaukos, Belkin, Bausch + Lomb, Zeiss, Character Biosciences, and Thea (consultant); Equinox (equity). Dr. Kiss: Adverum, Alcon, Novartis, Optos, and Genentech/Roche (consultant); Allergan, Novartis, Optos, Genentech/Roche, and Regeneron (research funding); Adverum, RegenxBio, and Fortress Bio (equity); gene therapy for age-related macular degeneration and T cells for CMV retinitis, assigned to Cornell University (intellectual property). Drs. D’Amico and Kiss reported that their consulting their consulting roles with Alcon had no bearing on the conception of this study, interpretation of the data retrieved from the MAUDE database, or composition of the manuscript. No discussion with third parties was held regarding the content of this manuscript, and the author(s) declared that their interpretation and analysis are solely their own. Authors with ongoing relationships with entities described in the manuscript were not involved in data acquisition, classification, or primary analysis. None of the other authors declared potential conflicts of interest with respect to the research, authorship, and/or publication of the article., (© The Author(s) 2024.)

Purpose: To report a technique to remove a dislocated ganciclovir implant in the vitreous cavity., Methods: Retrospective case series. Two patients with dislocated ganciclovir implants in the vitreous cavity., Results: A 6-mm pars plana incision was made; the soft tip was used to elevate the implant behind the intraocular lens and then 0.12-mm forceps were used to externalize the implant. The implant was successfully removed in both patients., Conclusion: Removal of a dislocated ganciclovir implant with its encasing strut can be effectively retrieved using a bimanual approach., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Aims: To characterise and classify the morphological, clinical and tomographic characteristics of focal choroidal excavation (FCE) lesions to determine their prognostic implications., Methods: 36 eyes with FCE (32 patients) underwent multimodal imaging, including spectral domain optical coherence tomography and fundus autofluorescence. FCE lesions were classified into three subtypes: (1) type 1: myopic (central choroidal thickness: <100 µm), (2) type 2: suspected congenital (central choroidal thickness: 100-200 µm, without associated chorioretinal pathology) and (3) type 3: secondary or acquired (central choroidal thickness: >200 µm, with associated chorioretinal pathology)., Results: 80.6% of eyes were followed longitudinally (26.8±18.8 months). There were 9 type 1 FCEs (myopic), 8 type 2 FCEs (U-shaped, congenital) and 19 type 3 FCEs (V-shaped, secondary). Type 2 FCEs trended towards larger maximum widths (p=0.0563). Type 3 FCEs were associated with central serous chorioretinopathy or pachyvessels (47.4%), but were also seen in pattern dystrophy, geographic atrophy, inactive choroiditis, torpedo maculopathy and adult-onset vitelliform dystrophy. Choroidal neovascular membranes (CNVMs) were more prevalent in type 3 FCE (41.2% compared with 11.1% for type 1 FCE, p=0.251, and 0% for type 2 FCE, p=0.043)., Conclusions: The FCE types, stratified by central choroidal thickness, demonstrated distinct morphological characteristics and associated findings. The classification scheme held prognostic implications as type 3 FCE with V shapes were associated with other chorioretinal conditions and were more likely to develop CNVM., Competing Interests: Competing interests: KK: consultant for Regenxbio. DD’A: consultant—Alcon, IVERIC bio and Aufbau Holdings; equity—IVERIC bio and Aufbau Holdings; intellectual property—Aufbau Holdings. Szilárd Kiss: consultant—Adverum, Alcon, Novartis, Optos and Genentech/Roche; research funding—Allergan, Novartis, Optos, Genentech/Roche and Regeneron; equity—Adverum, Regenxbio and Fortress Bio; intellectual property—gene therapy for age-related macular degeneration and T cells for CMV retinitis, assigned to Cornell University., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This work aims to review the principles of optical coherence tomography angiography (OCTA), to survey its clinical utility, and to highlight the strengths of this technology as well as barriers to adoption., Methods: A literature review with editorial discussion of the current applications for OCTA is presented., Results: There have been recent advances in multiple domains in OCTA imaging, including devices, algorithms, and new observations pertaining to a range of pathologies. New devices have improved the scanning speed, signal-to-noise ratio, and spatial resolution and offer an increased field of view. New algorithms have been proposed to optimize image processing and reduce artifacts. Numerous studies employing OCTA have been published describing changes to the microvasculature in diabetic retinopathy, age-related macular degeneration, central serous chorioretinopathy, retinal vein occlusion, and uveitis., Conclusions: OCTA provides noninvasive, high-resolution volumetric scans of the retinal and choroidal vasculature. OCTA can provide valuable data to augment traditional dye-based angiography in a range of chorioretinal diseases., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Purpose: This work aims to evaluate the clinical utility and feasibility of a novel scanning laser ophthalmoscope-based navigated ultra-widefield swept-source optical coherence tomography (UWF SS-OCT) imaging system., Methods: A retrospective, single-center, consecutive case series evaluated patients between September 2019 and October 2020 with UWF SS-OCT (modified Optos P200TxE, Optos PLC) as part of routine retinal care. The logistics of image acquisition, interpretability of images captured, nature of the peripheral abnormality, and clinical utility in management decisions were recorded., Results: Eighty-two eyes from 72 patients were included. Patients were aged 59.4 ± 17.1 years (range, 8-87 years). During imaging, 4.4 series of images were obtained in 4.1 minutes, with 86.4% of the image series deemed to be diagnostic of the peripheral pathology on blinded image review. The most common pathologic findings were chorioretinal scars (18 eyes). In 31 (38%) eyes, these images were meaningful in supporting clinical decision-making with definitive findings. Diagnoses imaged included retinal detachment combined with retinoschisis, retinal hole with overlying vitreous traction and subretinal fluid, vitreous inflammation overlying a peripheral scar, Coats disease, and peripheral retinal traction in sickle cell retinopathy., Conclusions: Navigated UWF SS-OCT imaging was clinically practical and provided high-quality characterization of peripheral retinal lesions for all eyes. Images directly contributed to management plans, including laser, injection or surgical treatment, for a clinically meaningful set of patients (38%). Future studies are needed to further assess the value of this imaging modality and its role in diagnosing, monitoring, and treating peripheral lesions., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.K. declared consulting and research funding from Optos (research funding was not received for the development of this study). He has also served as a consultant for Adverum, Alcon, Novartis, and Genentech/Roche; received research funding from Allergan, Novartis, Genentech/Roche, and Regeneron; received equity from Adverum, Regenxbio, and Fortress Bio; and intellectual property—gene therapy for age-related macular degeneration, and T cells for CMV retinitis—assigned to Cornell University. K.D.K. has served as a consultant for Regenxbio. D.J.D. has served as a consultant for Alcon, Iveric bio, and Aufbao Holdings; received equity from Iveric bio and Aufbau Holdings; and holds intellectual property for Aufbau Holdings. The other authors have nothing to declare., (© The Author(s) 2021.)

Objective: The central bouquet (CB) of the fovea comprises a dense array of cone photoreceptors intertwined with Müller cells. The aim of this investigation was to study visual outcomes and structural alterations in the foveal CB associated with cystoid macular edema (CME) of different etiologies., Design: Retrospective case series., Participants and Methods: This study analyzed eyes with various etiologies of CME, including diabetic macular edema, central retinal vein occlusion (CRVO), pseudophakic or Irvine-Gass (IG) syndrome, uveitis, and retinitis pigmentosa using spectral-domain optical coherence tomography (SD-OCT). SD-OCT was used to classify the CB alterations as either (1) thickened hyper-reflectivity associated with indistinct ellipsoid zone (EZ), or (2) subretinal fluid with intact EZ. Comparisons were made using the Students t test and Fisher's exact test., Results: The total cohort consisted of 61 eyes from 61 patients with various etiologies of CME. CB alterations were observed in 91% of uveitis eyes, 82% of CRVO eyes and 50% of IG eyes. Presence of CB alteration correlated with greater central macular thickness (p = 0.0020), horizontal extent of edema (p = 0.0042), and worse baseline visual acuity (p = 0.0195). Type 2 CB alterations were associated with worse logMAR vision compared with type 1 at baseline and final examinations (p = 0.0002, p = 0.0470)., Conclusions: CB alterations were noted in the majority of eyes with CME from CRVO, uveitis, and IG. The association observed between CB alterations and central macular thickness suggests that these alterations may develop as a result of mechanical stress of Müller cells on the CB., (Published by Elsevier Inc.)

Purpose: To evaluate structural features and visual outcomes in eyes with a prior history of laser treatment for retinopathy of prematurity (ROP)., Methods: Laser-treated eyes for type 1 ROP, preterm monitored eyes, and full-term control eyes were included. LogMAR conversion of Snellen best-corrected visual acuity and spherical equivalent based on cycloplegic refraction were measured in children 5-15 years of age. Anterior segment optical coherence tomography (OCT) was used to study structural features, including anterior chamber angle (ACA) in a subset of eyes., Results: A total of 50 eyes of 50 patients were included (19 full-term eyes, 19 laser-treated type 1 ROP eyes, 12 preterm monitored eyes). Of these, 44 eyes had visual outcomes data, and 15 eyes had anterior segment data. There was no significant difference in sex or age at final examination between the three groups. There was no significant difference in gestational age between the laser-treated and preterm monitored groups. Compared with the full-term control group and the preterm monitored group, the laser-treated ROP group had narrower ACA and more myopic refractive error. There was a significant correlation between ACA and spherical equivalent., Conclusions: Laser treatment may affect angle configuration in ROP eyes. Anterior segment OCT is an easy and useful modality that could aid in screening for visually impairing conditions such as myopia and glaucoma in children with ROP., (Copyright © 2020 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Recessive Stargardt disease (STGD1) is an inherited blinding disorder caused by mutations in the Abca4 gene. ABCA4 is a flippase in photoreceptor outer segments (OS) that translocates retinaldehyde conjugated to phosphatidylethanolamine across OS disc membranes. Loss of ABCA4 in Abca4 -/- mice and STGD1 patients causes buildup of lipofuscin in the retinal pigment epithelium (RPE) and degeneration of photoreceptors, leading to blindness. No effective treatment currently exists for STGD1. Here we show by several approaches that ABCA4 is additionally expressed in RPE cells. ( i ) By in situ hybridization analysis and by RNA-sequencing analysis, we show the Abca4 mRNA is expressed in human and mouse RPE cells. ( ii ) By quantitative immunoblotting, we show that the level of ABCA4 protein in homogenates of wild-type mouse RPE is about 1% of the level in neural retina homogenates. ( iii ) ABCA4 immunofluorescence is present in RPE cells of wild-type and Mertk -/- but not Abca4 -/- mouse retina sections, where it colocalizes with endolysosomal proteins. To elucidate the role of ABCA4 in RPE cells, we generated a line of genetically modified mice that express ABCA4 in RPE cells but not in photoreceptors. Mice from this line on the Abca4 -/- background showed partial rescue of photoreceptor degeneration and decreased lipofuscin accumulation compared with nontransgenic Abca4 -/- mice. We propose that ABCA4 functions to recycle retinaldehyde released during proteolysis of rhodopsin in RPE endolysosomes following daily phagocytosis of distal photoreceptor OS. ABCA4 deficiency in the RPE may play a role in the pathogenesis of STGD1., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Recessive Stargardt macular degeneration (STGD1) is caused by mutations in the gene for the ABCA4 transporter in photoreceptor outer segments. STGD1 patients and Abca4 -/- (STGD1) mice exhibit buildup of bisretinoid-containing lipofuscin pigments in the retinal pigment epithelium (RPE), increased oxidative stress, augmented complement activation and slow degeneration of photoreceptors. A reduction in complement negative regulatory proteins (CRPs), possibly owing to bisretinoid accumulation, may be responsible for the increased complement activation seen on the RPE of STGD1 mice. CRPs prevent attack on host cells by the complement system, and complement receptor 1-like protein y (CRRY) is an important CRP in mice. Here we attempted to rescue the phenotype in STGD1 mice by increasing expression of CRRY in the RPE using a gene therapy approach. We injected recombinant adeno-associated virus containing the CRRY coding sequence (AAV-CRRY) into the subretinal space of 4-wk-old Abca4 -/- mice. This resulted in sustained, several-fold increased expression of CRRY in the RPE, which significantly reduced the complement factors C3/C3b in the RPE. Unexpectedly, AAV-CRRY-treated STGD1 mice also showed reduced accumulation of bisretinoids compared with sham-injected STGD1 control mice. Furthermore, we observed slower photoreceptor degeneration and increased visual chromophore in 1-y-old AAV-CRRY-treated STGD1 mice. Rescue of the STGD1 phenotype by AAV-CRRY gene therapy suggests that complement attack on the RPE is an important etiologic factor in STGD1. Modulation of the complement system by locally increasing CRP expression using targeted gene therapy represents a potential treatment strategy for STGD1 and other retinopathies associated with complement dysregulation.

Purpose: To evaluate the safety of concurrent Boston type I keratoprosthesis (KPro) and glaucoma drainage device (GDD) implantation., Design: Retrospective comparative study of a consecutive cohort of patients., Subjects: Patients who underwent KPro implantation by a single surgeon (A.J.A.) with or without 1 concurrent Ahmed GDD (New World Medical, Inc., Rancho Cucamonga, CA) implantation between January 1, 2005, and January 31, 2015, were included. Patients with fewer than 3 months of follow-up or a history of previous KPro implantation were excluded., Methods: Preoperative, operative, and postoperative data were collected for each procedure. All comparisons were made between KPro procedures performed with or without concurrent GDD implantation. The Fisher exact test (2-tailed) was used to compare proportions, Student t test and Wilcoxon rank-sum test were used to compare means, and the log-rank test was used to compare time-to-outcome events., Main Outcome Measures: The primary outcome was frequency of the composite variable, that is, any serious vision-threatening postoperative complication, which included sterile vitreitis, endophthalmitis, hypotony maculopathy, suprachoroidal hemorrhage, retinal detachment, stromal necrosis, and infectious keratitis. Secondary outcomes included intraocular pressure control, worsening of visual acuity, cystoid macular edema, retroprosthetic membrane formation, persistent epithelial defect formation, GDD exposure, and KPro removal., Results: One hundred thirty-seven KPro procedures were performed in 129 patients: 91 (66.4%) KPro alone and 46 (33.6%) KPro plus GDD. There were no statistically significant differences between the 2 groups in terms of the incidence of vision-threatening postoperative complications. None of the 46 GDDs placed at the same time as the KPro became exposed during an average follow-up of 44 months., Conclusions: Compared with KPro alone, GDD placement combined with KPro was not associated with increased postoperative complications., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the multimodal imaging findings of posterior polar annular choroidal dystrophy (PPACD)., Methods: Retrospective case series of 2 patients diagnosed with PPACD. Spectral-domain optical coherence tomography, fundus autofluorescence, and fluorescein angiography findings of PPACD are described. Electroretinography results are also presented., Results: Both patients presented with bilateral peripapillary atrophy extending to involve the temporal arcades in an annular, foveal sparing pattern. Both cases demonstrated outer retinal atrophy with foveal sparing on spectral-domain optical coherence tomography, and fluorescein angiography illustrated corresponding window defects with late staining. Fundus autofluorescence showed hypoautofluorescence in the center of atrophic areas but hyperautofluorescence at the leading edge. Electroretinography findings included cone loss with rod preservation. Inflammatory and infectious workup was unremarkable in both cases., Conclusion: This report describes the multimodal imaging findings of a rare and poorly described chorioretinal disorder, PPACD, and will serve to guide clinicians regarding the evaluation and management of this elusive condition.

Purpose: To characterize the vascular structure of Type 3 neovascularization secondary to age-related macular degeneration using optical coherence tomography angiography., Methods: Optical coherence tomography angiography cube scans (3 mm × 3 mm) were acquired in 29 eyes of 24 patients with Type 3 lesions secondary to age-related macular degeneration using the RTVue XR Avanti with AngioVue, Split-spectrum amplitude-decorrelation, and motion correction technology. Automated layer segmentation boundaries were adjusted to best visualize the neovascular complex on en face projection images., Results: A distinct neovascular complex could be identified in 10 (34%) eyes, all of which were active on optical coherence tomography imaging. In all 10 eyes, the neovascular complex appeared as a small tuft of bright, high-flow tiny vessels with curvilinear morphology located in the outer retinal layers with a feeder vessel communicating with the inner retinal circulation (i.e., deep retinal capillary plexus). The mean (SD) size of the neovascular complex measured 0.07 (± 0.07) mm., Conclusion: With optical coherence tomography angiography, it is possible to identify small intraretinal neovascular complexes communicating with the deep retinal capillary plexus in eyes with Type 3 neovascularization secondary to age-related macular degeneration. Qualitative and quantitative analyses of Type 3 neovascular complexes can be performed using optical coherence tomography angiography.

Purpose: To analyze type 1 neovascular membranes in age-related macular degeneration (AMD) using optical coherence tomography (OCT) angiography, to correlate morphologic characteristics with imaging and clinical criteria, and to analyze structural features of type 1 neovascularization sequentially after anti-vascular endothelial growth factor (VEGF) therapy., Design: Prospective interventional case series., Methods: Macular OCT angiography images were acquired using the RTVue XR Avanti with AngioVue. Distinct morphologic patterns and quantifiable features of the neovascular membranes were studied on en face projection images at baseline and follow-up., Results: Thirty-three eyes of 25 patients were included. In 75% of the eyes, a highly organized vascular complex could be identified. A large main central vessel trunk/feeder vessel could be seen in 72% of these eyes, with vessels radiating in a branching pattern either in all directions from the center of the lesion ("medusa" pattern), or from one side of the lesion ("seafan" pattern). Of the 18 eyes with follow-up OCT angiography, the lesion area and vessel density remained unchanged, even after anti-vascular endothelial growth factor (VEGF) therapy, indicating a more mature longstanding neovascular complex resistant to anti-VEGF therapy., Conclusions: OCT angiography provides a unique opportunity to study the morphology of occult type 1 neovascular membranes in AMD and allows precise structural and vascular assessment noninvasively. We identified a large mature neovascular complex in approximately 75% of eyes, typically consisting of a feeder vessel and large branching vessels resistant to anti-VEGF therapy. OCT angiography may better guide evaluation and treatment of neovascular AMD, and may contribute to the development of improved therapies., (Copyright © 2015 Elsevier Inc. All rights reserved.)