BACILLARY LAYER DETACHMENT: MULTIMODAL IMAGING AND HISTOLOGIC EVIDENCE OF A NOVEL OPTICAL COHERENCE TOMOGRAPHY TERMINOLOGY: Literature Review and Proposed Theory.

PURPOSE: To clarify the histologic basis of bacillary layer detachment (BALAD) through a review of the current literature and an analysis of retinal imaging. METHODS: The literature for previous reports of BALAD were reviewed. An analysis of retinal images was performed to support anatomical conclusions. RESULTS: A total of 164 unique patients with BALAD on optical coherence tomography (OCT) were identified from the published literature. Twenty-two underlying etiologies, all associated with subretinal exudation, were identified. Forty-one different OCT terminologies were found. The defining OCT feature of BALAD was a split at the level of the photoreceptor inner segment myoid creating a distinctive intraretinal cavity. Resolution of BALAD was followed by a rapid restoration of the ellipsoid zone. Histology of age-related macular degeneration eyes suggests that individual photoreceptors can shed inner segments. Furthermore, detachment of the entire layer of inner segments is a common postmortem artifact. It is proposed that BALAD occurs when outwardly directed forces promoting attachment of photoreceptor outer segments to the retinal pigment epithelium exceed the tensile strength of the photoreceptor inner segment myoid. CONCLUSION: This review serves to strengthen the OCT nomenclature "bacillary layer detachment," based on specific reflectance information obtained by OCT and previously published histologic observations.

Intravitreous Cutaneous Metastatic Melanoma in the Era of Checkpoint Inhibition: Unmasking and Masquerading.

PURPOSE: Cutaneous melanoma metastatic to the vitreous is very rare. This study investigated the clinical findings, treatment, and outcome of patients with metastatic cutaneous melanoma to the vitreous. Most patients received checkpoint inhibition for the treatment of systemic disease, and the significance of this was explored. DESIGN: Multicenter, retrospective cohort study. PARTICIPANTS: Fourteen eyes of 11 patients with metastatic cutaneous melanoma to the vitreous. METHODS: Clinical records, including fundus photography and ultrasound results, were reviewed retrospectively, and relevant data were recorded for each patient eye. MAIN OUTCOME MEASURES: Clinical features at presentation, ophthalmic and systemic treatments, and outcomes. RESULTS: The median age at presentation of ophthalmic disease was 66 years (range, 23-88 years), and the median follow-up from diagnosis of ophthalmic disease was 23 months. Ten of 11 patients were treated with immune checkpoint inhibition at some point in the treatment course. The median time from starting immunotherapy to ocular symptoms was 17 months (range, 4.5-38 months). Half of eyes demonstrated amelanotic vitreous debris. Five eyes demonstrated elevated intraocular pressure, and 4 eyes demonstrated a retinal detachment. Six patients showed metastatic disease in the central nervous system. Ophthalmic treatment included external beam radiation (30-40 Gy) in 6 eyes, intravitreous melphalan (10-20 µg) in 4 eyes, enucleation of 1 eye, and local observation while receiving systemic treatment in 2 eyes. Three eyes received intravitreous bevacizumab for neovascularization. The final Snellen visual acuity ranged from 20/20 to no light perception. CONCLUSIONS: The differential diagnosis of vitreous debris in the context of metastatic cutaneous melanoma includes intravitreal metastasis, and this seems to be particularly apparent during this era of treatment with checkpoint inhibition. External beam radiation, intravitreous melphalan, and systemic checkpoint inhibition can be used in the treatment of ophthalmic disease. Neovascular glaucoma and retinal detachments may occur, and most eyes show poor visual potential. Approximately one quarter of patients demonstrated ocular disease that preceded central nervous system metastasis. Patients with visual symptoms or vitreous debris in the context of metastatic cutaneous melanoma would benefit from evaluation by an ophthalmic oncologist.

In vivo imaging of the fibrillar architecture of the posterior vitreous and its relationship to the premacular bursa, Cloquet's canal, prevascular vitreous fissures, and cisterns.

PURPOSE: To describe the fibrillar architecture of the posterior cortical vitreous and identify variations across eyes of different axial lengths in vivo. METHODS: Sixty-four eyes of 32 subjects were examined with swept-source optical coherence tomography (SS-OCT). Grading of vitreous degeneration, presence of vitreous cisterns/lacunae, posterior hyaloid status, directionality of vitreous fibers and their relations to vitreous spaces, and lamellar reflectivity of the posterior vitreous were assessed. RESULTS: A consistent pattern of fibrillar organization was discovered. Eyewall parallel fibers formed a dense meshwork over the retinal surface and fibers oriented in a perpendicular fashion to this meshwork were found to envelop the various vitreous spaces, intersecting at variable angles of insertion to the eyewall parallel fibers. Lamellar reflectivity suggestive of splitting of the cortical fibrillar meshwork was detected in 27 eyes (42%) with 56% of these eyes demonstrating perpendicularly oriented intersecting fibers. Fifty-six percent of eyes with lamellar reflectivity had an axial length > 25 mm. CONCLUSION: SS-OCT imaging revealed fibrillar organization of the posterior vitreous. Eye wall parallel hyperreflectivity of cortical vitreous was a universal finding. This pattern is suggestive of a splitting of cortical vitreous tissue and may represent a precursor to vitreoschisis. Perpendicular fibers appear to be important constituents of the walls of the various liquid vitreous spaces.

Clinical outcomes and antibiotic susceptibilities of Staphylococcus aureus endophthalmitis.

PURPOSE: To compare the antibiotic susceptibilities and visual acuity (VA) outcomes in endophthalmitis caused by methicillin-resistant (MRSA) versus methicillin-sensitive S. aureus (MSSA). METHODS: The records of 34 cases of S. aureus endophthalmitis at The New York Eye and Ear Infirmary from Jan 1997 to June 2011 were reviewed. Antibiotic susceptibility profiles over time and VA at presentation and at 3, 6, and ≥12 months were recorded. S. aureus isolates were grouped based on oxacillin resistance. RESULTS: Of the 34 cases, 15 (44 %) were MRSA and 19 (56 %) MSSA. Median presenting VA was hand motions (logMAR 4.0) in both the MRSA and MSSA groups. There was no statistically significant difference in VA between the MRSA and MSSA groups at 3, 6, or ≥12 months. No MRSA isolates were resistant to vancomycin or gentamicin. While over 85 % of MRSA isolates tested for fourth-generation fluoroquinolones were resistant, just 10 % MSSA isolates tested were resistant. There was a trend suggesting an increase in the proportion of MRSA isolates compared to MSSA isolates over the course of the study period. CONCLUSIONS: There was no statistical difference in short- or long-term VA outcomes between the MRSA and MSSA groups at any time point. Resistance to fourth-generation fluoroquinolones was present in over 85 % of MRSA isolates, but just 10 % of MSSA isolates. An increasing proportion of MRSA amongst S. aureus isolates was noted over the course of the study period.

TOMOGRAPHIC RELATIONSHIPS BETWEEN RETINAL NEOVASCULARIZATION AND THE POSTERIOR VITREOUS IN PROLIFERATIVE DIABETIC RETINOPATHY.

PURPOSE: To describe anatomical relationships of retinal neovascular complexes (NVCs) and the posterior vitreous in proliferative diabetic retinopathy using spectral domain optical coherence tomography. METHODS: Cross-sectional study. Neovascular complexes were imaged using spectral domain optical coherence tomography in 51 eyes of 37 patients. The relationship of NVCs to the posterior vitreous cortex and posterior vitreous spaces, such as the premacular bursa, prevascular vitreous fissures, and perimacular cisterns, was analyzed. RESULTS: In the 77 NVCs evaluated, 61 (79%) had grown along the outer surface of the posterior hyaloid face, and vitreoschisis was present in 37 (48%). The "wolf's jaw" configuration was present in 9% and resulted from NVC arising from the arcades and proliferating along the posterior hyaloid face. By contrast, NVCs that invaded the bursa originated from smaller venous tributaries more distant from the arcades. The premacular bursa and prevascular vitreous fissure/perimacular cistern were invaded infrequently, respectively, in 15% and 38% (P = 0.137). CONCLUSION: Tomographic analysis of diabetic NVCs showed that most NVCs arise and grow along the posterior hyaloid face and that vitreoschisis is more prevalent than what has been found in ultrasound studies. The wolf's jaw configuration does not seem to result from the invasion of the bursa, as previously suggested.

ASSOCIATION OF PREVASCULAR VITREOUS FISSURES AND CISTERNS WITH VITREOUS DEGENERATION AS ASSESSED BY SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To demonstrate the presence of prevascular vitreous fissures (PVF) and posterior vitreous cisterns in vivo and correlate with the degree of vitreous degeneration (VD). METHODS: This was a cross-sectional study using Topcon Deep Range Imaging OCT-1 Atlantis 3D swept source optical coherence tomography for acquiring scans of posterior vitreous covering an 18 × 18-mm area in 104 eyes of 52 healthy volunteers without posterior vitreous detachment. RESULTS: We observed that increasing age was associated with higher VD grades (P < 0.05). Prevascular vitreous fissures, characterized by areas of lower optical density overlying the retinal blood vessels, were identified in 93 (89%) eyes, and the presence of PVF correlated with lower VD grades (P < 0.05). Presence of cisterns correlated with higher VD grades (P < 0.05). All eyes with absence of PVF were found to have established cisterns. Prevascular vitreous fissures were connected with cisterns in 44 of the 71 (62%) eyes with cisterns, while the base of the cistern was directly above retinal blood vessels in 38 (54%) eyes, which suggests that the cisterns could be derived from PVF. CONCLUSION: Swept source optical coherence tomography imaging can identify PVF and cisterns occurring in the context of age-related VD, and PVF appeared to be possible precursors of cisterns.

The premacular bursa's shape revealed in vivo by swept-source optical coherence tomography.

OBJECTIVE: To resolve the controversy surrounding the shape and relationship of posterior vitreous spaces by characterizing the connections between the premacular bursa, the area of Martegiani, and Cloquet's canal. DESIGN: Comprehensive posterior vitreous maps were created using swept-source optical coherence tomography (SS OCT) in a cross-sectional study. PARTICIPANTS: The posterior vitreous of 102 eyes of 51 volunteers 21 to 54 years of age without ocular pathologic features was imaged using SS OCT. METHODS: The DRI OCT-1 Atlantis 3D SS OCT (Topcon Medical Systems, Oakland, NJ) was used to acquire scans of the posterior vitreous over an 18×18-mm area. MAIN OUTCOME MEASURES: Posterior vitreous spaces and their relationships were identified. RESULTS: The premacular bursa was identified in all 102 eyes and was found to extend superiorly beyond our scanning ability at a variable angle. No discernible superior borders could be identified. Instead, a connection of the bursa with the preoptic area of Martegiani or its extension, Cloquet's canal, was found in 101 of 102 eyes. This connection occurred at a variable distance from the optic nerve, where it formed a flat and broad superior channel. The skyward direction of this channel was found to be gravity dependent in all 14 eyes of the 7 subjects examined in various head positions. Although SS OCT was able to identify vitreous degeneration, the above changes were present in 28 eyes even without any discernible vitreous degeneration. CONCLUSIONS: The premacular bursa, also called the posterior precortical vitreous pocket, was found to continue superiorly beyond the posterior pole without a detectable border. The bursa fused broadly with the extension of the preoptic area of Martegiani, namely Cloquet's canal, or the hyaloidal tract of Eisner. These findings suggest that there is a direct anteroposterior connection between the retrolental and premacular and preoptic spaces already existent in the eyes of young adults before the occurrence of vitreous degeneration. This observation may have important implications with respect to the movement of intrinsic and extrinsic mediators between the anterior and posterior segments.

Microbiological spectrum and antibiotic sensitivity in endophthalmitis: a 25-year review.

PURPOSE: To identify the spectrum and susceptibility pattern of pathogens responsible for culture-positive endophthalmitis referred to a single institution and investigate possible trends in both pathogens and antibiotic sensitivities over the past 25 years. DESIGN: A retrospective, laboratory-based study of consecutive microbiological isolates. PARTICIPANTS: A total of 988 consecutive culture-positive endophthalmitis isolates from 911 eyes. METHODS: All culture-positive endophthalmitis isolates collected from 1987 to 2011 were identified. Susceptibility rates to a variety of antibiotics were calculated. Chi-square test for trend was used to detect changes in spectrum or susceptibility over time. MAIN OUTCOME MEASURES: Microbial spectrum and susceptibility pattern over time. RESULTS: A total of 988 isolates were identified from 911 eyes. The average patient age was 67 ± 18 years, and 55% of the patients were female. The most prevalent pathogens were coagulase-negative staphylococcus (39.4%), followed by Streptococcus viridans species (12.1%) and Staphylococcus aureus (11.1%). Gram-negative organisms and fungi accounted for 10.3% and 4.6% of all isolates, respectively. With the exception of 2 isolates, Enterococcus faecium and Nocardia exalbida, all the other 725 (99.7%) gram-positive bacteria tested were susceptible to vancomycin. Of the 94 gram-negative organisms tested against ceftazidime, 2 were of intermediate sensitivity and 6 were resistant. For 8 antibiotics, increasing microbial resistance over time was observed: cefazolin (P = 0.02), cefotetan (P = 0.006), cephalothin (P<0.0001), clindamycin (P = 0.04), erythromycin (P<0.0001), methicillin/oxacillin (P<0.0001), ampicillin (P = 0.01), and ceftriaxone (P = 0.006). For 3 antibiotics, increasing microbial susceptibility was observed: gentamicin (P<0.0001), tobramycin (P = 0.005), and imipenem (P<0.0001). CONCLUSIONS: Coagulase-negative staphylococcus remains the most frequently identified cause of endophthalmitis. Vancomycin and ceftazidime seem to be excellent empiric antibiotics for treating endophthalmitis. Although a statistically significant trend toward increasing microbial resistance against a variety of antibiotics, including cephalosporins and methicillin, was observed, a significant trend toward decreasing microbial resistance against aminoglycosides and imipenem also was detected.

Polypoidal choroidal vasculopathy: simultaneous indocyanine green angiography and eye-tracked spectral domain optical coherence tomography findings.

PURPOSE: To describe simultaneous scanning laser ophthalmoscope indocyanine green angiographic and eye-tracked spectral-domain optical coherence tomography findings in eyes with polypoidal choroidal vasculopathy (PCV). METHODS: Eighteen eyes of 18 patients with PCV because of a variety of different diagnoses were imaged with simultaneous scanning laser ophthalmoscope indocyanine green angiography and eye-tracked spectral-domain optical coherence tomography to localize the polyps and their associated vascular structures with respect to the retinal layers. RESULTS: Regardless of the underlying diagnosis, simultaneous scanning laser ophthalmoscope indocyanine green angiography and eye-tracked spectral-domain optical coherence tomography imaging localized the polypoidal structures of PCV to within larger Type 1 neovascular complexes occurring within or above Bruch membrane. In 8 eyes, PCV appeared to adhere to the undersurface of an elevated retinal pigment epithelial detachment. In 1 eye, a PCV lesion was detected within the neurosensory retina having apparently eroded through the overlying retinal pigment epithelium. CONCLUSION: Simultaneous scanning laser ophthalmoscope indocyanine green angiography and eye-tracked spectral-domain optical coherence tomography demonstrate that a majority of PCV represents a variant of the Type 1 neovascular growth pattern, which can occur in a variety of different neovascularized maculopathies. Polypoidal choroidal vasculopathy lesions appear to originate from long-standing choroidal neovascularization, rather than from the choroidal vasculature itself. Given these observations, PCV would be more accurately described as a neovasculopathy rather than as a choroidal vasculopathy.

A Pixel-Based Machine-Learning Model For Three-Dimensional Reconstruction of Vitreous Anatomy.

Purpose: To develop a machine-learning image processing model for three-dimensional (3D) reconstruction of vitreous anatomy visualized with swept-source optical coherence tomography (SS-OCT). Methods: Healthy subjects were imaged with SS-OCT. Scans of sufficient quality were transferred into the Fiji is just ImageJ image processing toolkit, and proportions of the resulting stacks were adjusted to form cubic voxels. Image-averaging and Trainable Weka Segmentation using Sobel and variance edge detection and directional membrane projections filters were used to enhance and interpret the signals from vitreous gel, liquid spaces within the vitreous, and interfaces between the former. Two classes were defined: "Septa" and "Other." Pixels were selected and added to each class to train the classifier. Results were generated as a probability map. Thresholding was performed to remove pixels that were classified with low confidence. Volume rendering was performed with TomViz. Results: Forty-seven eyes of 34 healthy subjects were imaged with SS-OCT. Thirty-four cube scans from 25 subjects were of sufficient quality for volume rendering. Clinically relevant vitreous features including the premacular bursa, area of Martegiani, and prevascular vitreous fissures and cisterns, as well as varying degrees of vitreous degeneration were visualized in 3D. Conclusions: A machine-learning model for 3D vitreous reconstruction of SS-OCT cube scans was developed. The resultant high-resolution 3D movies illustrated vitreous anatomy in a manner like triamcinolone-assisted vitrectomy or postmortem dye injection. Translational Relevance: This machine learning model now allows for comprehensive examination of the vitreous structure beyond the vitreoretinal interface in 3D with potential applications for common disease states such as the vitreomacular traction and Macular Hole spectrum of diseases or proliferative diabetic retinopathy.

Hyalocyte origin, structure, and imaging.

Introduction: Hyalocytes have been recognized as resident tissue macrophages of the vitreous body since the mid-19th century. Despite this, knowledge about their origin, turnover, and dynamics is limited. Areas covered: Historically, initial studies on the origin of hyalocytes used light and electron microscopy. Modern investigations across species including rodents and humans will be described. Novel imaging is now available to study human hyalocytes in vivo. The shared ontogeny with retinal microglia and their eventual interdependence as well as differences will be discussed. Expert opinion: Owing to a common origin as myeloid cells, hyalocytes and retinal microglia have similarities, but hyalocytes appear to be distinct as resident macrophages of the vitreous body.

Hyalocytes in proliferative vitreo-retinal diseases.

Introduction: Hyalocytes are sentinel macrophages residing within the posterior vitreous cortex anterior to the retinal inner limiting membrane (ILM). Following anomalous PVD and vitreoschisis, hyalocytes contribute to paucicellular (vitreo-macular traction syndrome, macular holes) and hypercellular (macular pucker, proliferative vitreo-retinopathy, proliferative diabetic vitreo-retinopathy) diseases. Areas covered: Studies of human tissues employing dark-field, phase, and electron microscopy; immunohistochemistry; and in vivo imaging of human hyalocytes. Expert opinion: Hyalocytes are important in early pathophysiology, stimulating cell migration and proliferation, as well as subsequent membrane contraction and vitreo-retinal traction. Targeting hyalocytes early could mitigate advanced disease. Ultimately, eliminating the role of vitreous and hyalocytes may prevent proliferative vitreo-retinal diseases entirely.

Correlation between Macular Neovascularization (MNV) Type and Druse Type in Neovascular Age-Related Macular Degeneration (AMD) Based on the CONAN Classification.

To investigate associations and predictive factors between macular neovascularization (MNV) lesion variants and drusen types in patients with treatment-naïve neovascular age-related macular degeneration (AMD). Methods: Multimodal imaging was retrospectively reviewed for druse type (soft drusen, subretinal drusenoid deposits (SDDs) or mixed) and MNV type (MNV 1, MNV 2, MNV 1/2 or MNV 3). The Consensus on Neovascular AMD Nomenclature (CONAN) classification was used for characterizing MNV at baseline. Results: One eye of each eligible patient was included (n = 191). Patients with predominant SDDs had an increased adjusted odds ratio (aOR) for MNV 2 (23.4453, p = 0.0025) and any type of MNV 3 (8.7374, p < 0.0001). Patients with MNV 1/2 had an aOR for predominant SDDs (0.3284, p = 0.0084). Patients with MNV1 showed an aOR for SDDs (0.0357, p < 0.0001). Eyes with SDDs only without other drusen types showed an aOR for MNV 2 (9.2945, p < 0.0001). Conclusions: SDDs represent a common phenotypic characteristic in AMD eyes with treatment-naïve MNV. The aOR for eyes with predominant SDDs to develop MNV 2 and MNV 3 was much higher, possibly due to their location in the subretinal space. The predominant druse type may help to predict which type of MNV will develop during the course of AMD.

Update on Optical Coherence Tomography and Optical Coherence Tomography Angiography Imaging in Proliferative Diabetic Retinopathy.

Proliferative diabetic retinopathy (PDR) is a major cause of blindness in diabetic individuals. Optical coherence tomography (OCT) and OCT-angiography (OCTA) are noninvasive imaging techniques useful for the diagnosis and assessment of PDR. We aim to review several recent developments using OCT and discuss their present and potential future applications in the clinical setting. An electronic database search was performed so as to include all studies assessing OCT and/or OCTA findings in PDR patients published from 1 January 2020 to 31 May 2021. Thirty studies were included, and the most recently published data essentially focused on the higher detection rate of neovascularization obtained with widefield-OCT and/or OCTA (WF-OCT/OCTA) and on the increasing quality of retinal imaging with quality levels non-inferior to widefield-fluorescein angiography (WF-FA). There were also significant developments in the study of retinal nonperfusion areas (NPAs) using these techniques and research on the impact of PDR treatment on NPAs and on vascular density. It is becoming increasingly clear that it is critical to use adequate imaging protocols focused on optimized segmentation and maximized imaged retinal area, with ongoing technological development through artificial intelligence and deep learning. These latest findings emphasize the growing applicability and role of noninvasive imaging in managing PDR with the added benefit of avoiding the repetition of invasive conventional FA.