SARS-CoV-2 vaccination in the first year after hematopoietic cell transplant or chimeric antigen receptor T cell therapy: A prospective, multicenter, observational study.

BACKGROUND: The optimal timing of vaccination with SARS-CoV-2 vaccines after cellular therapy is incompletely understood. The objectives of this study are to determine whether humoral and cellular responses after SARS-CoV-2 vaccination differ if initiated <4 months versus 4-12 months after cellular therapy. METHODS: We conducted a multicenter prospective observational study at 30 cancer centers in the United States. SARS-CoV-2 vaccination was administered as part of routine care. We obtained blood prior to and after vaccinations at up to five time points and tested for SARS-CoV-2 spike (anti-S) IgG in all participants and neutralizing antibodies for Wuhan D614G, Delta B.1.617.2, and Omicron B.1.1.529 strains, as well as SARS-CoV-2-specific T cell receptors (TCRs), in a subgroup. RESULTS: We enrolled 466 allogeneic hematopoietic cell transplant (HCT; n=231), autologous HCT (n=170), and chimeric antigen receptor T cell (CAR-T cell) therapy (n=65) recipients between April 2021 and June 2022. Humoral and cellular responses did not significantly differ among participants initiating vaccinations <4 months vs 4-12 months after cellular therapy. Anti-S IgG ≥2,500 U/mL was correlated with high neutralizing antibody titers and attained by the last time point in 70%, 69%, and 34% of allogeneic HCT, autologous HCT, and CAR-T cell recipients, respectively. SARS-CoV-2-specific T cell responses were attained in 57%, 83%, and 58%, respectively. Pre-cellular therapy SARS-CoV-2 infection or vaccination were key predictors of post-cellular therapy immunity. CONCLUSIONS: These data support mRNA SARS-CoV-2 vaccination prior to, and reinitiation three to four months after, cellular therapies with allogeneic HCT, autologous HCT, and CAR-T cell therapy.

Long-term Visual Outcomes and Causes of Vision Loss in Chronic Central Serous Chorioretinopathy.

PURPOSE: To evaluate the long-term visual outcomes and causes of vision loss in chronic central serous chorioretinopathy (CSC). DESIGN: Retrospective, longitudinal study. PARTICIPANTS: A total of 133 participants (217 eyes) with chronic CSC. METHODS: A retrospective review of clinical and multimodal imaging data of patients with chronic CSC managed by 3 of the authors between May 1977 and March 2018. Multimodal imaging comprised color photography, fluorescein angiography, indocyanine green angiography, fundus autofluorescence (FAF), and OCT. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) at the final visit; change in BCVA between first visit and 1-, 5-, and 10-year follow-up visits; and causes of vision loss at final visit. RESULTS: Data from 6228 individual clinic visits were analyzed. Mean age of patients at the first visit was 60.7 years, and mean period of follow-up from first to last visit was 11.3 years. The cohort included 101 male patients (75.9%). At the final visit, 106 patients (79.7%) maintained driving-standard vision with BCVA of 20/40 or better in at least 1 eye, and 17 patients (12.8%) were legally blind with BCVA of 20/200 or worse in both eyes. Mean BCVA at first visit was not significantly different from mean BCVA at 1- or 5-year follow-up visits (both P ≥ 0.65) but was significantly better than the mean BCVA at the 10-year follow-up visit (P = 0.04). Seventy-nine percent of eyes with 20/40 or better vision at the first visit maintained the same level of vision at the 10-year follow-up visit. Ninety-two percent of eyes with 20/200 or worse vision at the first visit maintained the same level of vision at the 10-year follow-up visit. Cystoid macular degeneration, choroidal neovascularization (CNV), outer retinal disruption on OCT, and FAF changes were associated with poorer vision at the final visit (all P ≤ 0.001). Multivariable analysis revealed that greater age at first visit was associated with greater BCVA change at the 10-year follow-up visit (P = 0.001). CONCLUSIONS: Chronic CSC can be a sight-threatening disease leading to legal blindness. Age at presentation and outer retinal changes on multimodal imaging were associated with long-term BCVA changes and may be predictors of long-term visual outcomes.

Vision Loss from Choroidal and Pituitary Metastases Secondary to Renal Cell Carcinoma: A Case Report.

A 62-year-old male with a history of metastatic clear cell renal cell carcinoma (ccRCC) presented with decreased vision to 20/50 in the left eye. Fundus examination revealed an elevated, amelanotic mass lesion in the superotemporal macula, without involvement of the central macula by subretinal fluid or tumour. Given incongruity between the fundus findings and the degree of visual impairment, visual field testing was obtained, revealing a bitemporal hemianopia. Magnetic resonance imaging demonstrated optic chiasm compression by a pituitary mass, which had previously been overlooked on computed tomography imaging. Biopsy confirmed metastatic ccRCC to the pituitary, which presented simultaneously with the presumed choroidal metastasis.

Phytase production by solid-state fermentation of groundnut oil cake by Aspergillus niger: A bioprocess optimization study for animal feedstock applications.

This investigation deals with the use of agro-industrial waste, namely groundnut oil cake (GOC), for phytase production by the fungi Aspergillus niger NCIM 563. Plackett-Burman design (PBD) was used to evaluate the effect of 11 process variables and studies here showed that phytase production was significantly influenced by glucose, dextrin, distilled water, and MgSO4 · 7H2O. The use of response surface methodology (RSM) by Box-Behnken design (BBD) of experiments further enhanced the production by a remarkable 36.67-fold from the original finding of 15 IU/gds (grams of dry substrate) to 550 IU/gds. This is the highest solid-state fermentation (SSF) phytase production reported when compared to other microorganisms and in fact betters the best known by a factor of 2. Experiments carried out using dried fermented koji for phosphorus and mineral release and also thermal stability have shown the phytase to be as efficient as the liquid enzyme extract. Also, the enzyme, while exhibiting optimal activity under acidic conditions, was found to have significant activity in a broad range of pH values (1.5-6.5). The studies suggest the suitability of the koji supplemented with phytase produced in an SSF process by the "generally regarded as safe" (GRAS) microorganism A. niger as a cost-effective value-added livestock feed when compared to that obtained by submerged fermentation (SmF).

Type 3 neovascularization: evolution, association with pigment epithelial detachment, and treatment response as revealed by spectral domain optical coherence tomography.

PURPOSE: To demonstrate the evolution and treatment response of Type 3 neovascularization using spectral domain optical coherence tomography. METHODS: We retrospectively analyzed 40 eyes treated with intravitreal anti-vascular endothelial growth factor therapy for Type 3 neovascularization over a variable follow-up period. RESULTS: In 17 eyes, spectral domain optical coherence tomography captured the development of Type 3 neovascularization from punctate hyperreflective foci that preceded any outer retinal defect. The more mature Type 3 lesions were associated with outer retinal disruption and adjacent cystoid macular edema. In addition, 37 of 40 Type 3 lesions (93%) were associated with an underlying pigment epithelial detachment, of which 26 (70%) were drusenoid, 6 (16%) serous, and 5 (14%) mixed. Type 3 vessels appeared to leak fluid into the pigment epithelial detachment cavity, creating serous pigment epithelial detachments as large as 925 µm in maximal height. Treatment with anti-vascular endothelial growth factor agents led to prompt involution of the lesion and resorption of the intraretinal and subretinal pigment epithelium fluid after one or two injections (median = 1). CONCLUSION: In some eyes with age-related macular degeneration, the earliest sign of Type 3 neovascularization is punctate hyperreflective foci above the external limiting membrane. The mature Type 3 lesions and associated serous pigment epithelial detachments are highly responsive to anti-vascular endothelial growth factor therapy.

Choroidal thickness in retinal pigment epithelial tear as measured by spectral domain optical coherence tomography.

PURPOSE: To evaluate the choroidal thickness with spectral domain optical coherence tomography in subjects with retinal pigment epithelial (RPE) tear compared with the choroidal thickness of their fellow eye. METHODS: For this cross-sectional investigation, seven eyes of seven patients with neovascular age-related macular degeneration and RPE tear in one eye imaged with spectral domain optical coherence tomography were identified. Choroidal thickness was measured from the posterior edge of the retinal pigment epithelium to the choroid/sclera junction at 500 µm intervals up to 2,500 µm temporal and nasal to the fovea in both the eye with the RPE tear and the eye with intact RPE. All measurements were performed by two independent observers and averaged for the purpose of the analysis. Measurements were compared using paired t-test. RESULTS: The average age of patients was 79 years (range, 66-88 years). All subjects had dome-shaped pigment epithelial detachments before RPE tear and no dome-shaped pigment epithelial detachments in the unaffected eye. Average subfoveal choroidal thickness in the eye with the RPE tear was 154.9 ± 10.1 µm. Average subfoveal choroidal thickness in the eye with intact RPE was 212.9 ± 10.6 µm (P = 0.035). CONCLUSION: There is a significant decrease in subfoveal choroidal thickness in the subjects with RPE tear compared with their fellow eye with intact RPE. It is unclear if this thinning is a consequence of or precedes the RPE tear. Further studies are necessary to prospectively follow choroidal thickness in subjects with dome-shaped pigment epithelial detachments.

SARS-CoV-2 vaccination in the first year after hematopoietic cell transplant or chimeric antigen receptor T cell therapy: A prospective, multicenter, observational study (BMT CTN 2101).

Background: The optimal timing of vaccination with SARS-CoV-2 vaccines after cellular therapy is incompletely understood. Objective: To describe humoral and cellular responses after SARS-CoV-2 vaccination initiated <4 months versus 4-12 months after cellular therapy. Design: Multicenter prospective observational study. Setting: 34 centers in the United States. Participants: 466 allogeneic hematopoietic cell transplant (HCT; n=231), autologous HCT (n=170), or chimeric antigen receptor T cell (CAR-T cell) therapy (n=65) recipients enrolled between April 2021 and June 2022. Interventions: SARS-CoV-2 vaccination as part of routine care. Measurements: We obtained blood prior to and after vaccinations at up to five time points and tested for SARS-CoV-2 spike (anti-S) IgG in all participants and neutralizing antibodies for Wuhan D614G, Delta B.1.617.2, and Omicron B.1.1.529 strains, as well as SARS-CoV-2-specific T cell receptors (TCRs), in a subgroup. Results: Anti-S IgG and neutralizing antibody responses increased with vaccination in HCT recipients irrespective of vaccine initiation timing but were unchanged in CAR-T cell recipients initiating vaccines within 4 months. Anti-S IgG ≥2,500 U/mL was correlated with high neutralizing antibody titers and attained by the last time point in 70%, 69%, and 34% of allogeneic HCT, autologous HCT, and CAR-T cell recipients, respectively. SARS-CoV-2-specific T cell responses were attained in 57%, 83%, and 58%, respectively. Humoral and cellular responses did not significantly differ among participants initiating vaccinations <4 months vs 4-12 months after cellular therapy. Pre-cellular therapy SARS-CoV-2 infection or vaccination were key predictors of post-cellular therapy anti-S IgG levels. Limitations: The majority of participants were adults and received mRNA vaccines. Conclusions: These data support starting mRNA SARS-CoV-2 vaccination three to four months after allogeneic HCT, autologous HCT, and CAR-T cell therapy. Funding: National Marrow Donor Program, Leukemia and Lymphoma Society, Multiple Myeloma Research Foundation, Novartis, LabCorp, American Society for Transplantation and Cellular Therapy, Adaptive Biotechnologies, and the National Institutes of Health.

Effect of phytase from Aspergillus niger on plant growth and mineral assimilation in wheat (Triticum aestivum Linn.) and its potential for use as a soil amendment.

BACKGROUND: Extensive use of non-replenishable phosphate reserves as phosphate supplements in agriculture and animal feed poses a threat for environmental pollution and necessitated a search for alternative phosphate sources. Unlocking the phytate phosphorus using microbial phytase can provide an ecofriendly solution in agriculture. The aim of the present work was to evaluate the effect of phytase from Aspergillus niger NCIM 563 in degradation of phytate phosphorus to benefit plant nutrition and soil amendment in comparison with chemical fertilizers. RESULTS: An enzyme dose of 12 IU was sufficient to hydrolyze phytate and increase assimilation of phosphorus by about 74%. Phytase supplementation leads to increase in shoot:total length ratio by about 200%, indicating its growth-promoting effect. Consistency in phytase-induced growth was reflected at pot and tray levels, wherein shoot:total length ratio was observed to be 2.01 and 2.12 respectively. Mineral assimilation due to phytase was more efficient as compared to chemical fertilizers, thus overcoming the constraints of practicability and economics in the agriculture industry. Phytase was efficient in reducing the phytic acid content of soil by about 30% while simultaneously increasing the phytate phosphate availability by 1.18-fold. CONCLUSION: Phytase from A. niger showed improvement in phytate phosphorus and mineral availability. Besides a plant growth-promoting effect, reduction in use of chemical fertilizers and soil improvement could be achieved simultaneously for maintaining the sustainability of agriculture.

SARS-CoV-2 vaccination in the first year after allogeneic hematopoietic cell transplant: a prospective, multicentre, observational study.

Background: The optimal timing for SARS-CoV-2 vaccines within the first year after allogeneic hematopoietic cell transplant (HCT) is poorly understood. Methods: We conducted a prospective, multicentre, observational study of allogeneic HCT recipients who initiated SARS-CoV-2 vaccinations within 12 months of HCT. Participants were enrolled at 22 academic cancer centers across the United States. Participants of any age who were planning to receive a first post-HCT SARS-CoV-2 vaccine within 12 months of HCT were eligible. We obtained blood prior to and after each vaccine dose for up to four vaccine doses, with an end-of-study sample seven to nine months after enrollment. We tested for SARS-CoV-2 spike protein (anti-S) IgG; nucleocapsid protein (anti-N) IgG; neutralizing antibodies for Wuhan D614G, Delta B.1.617.2, and Omicron B.1.1.529 strains; and SARS-CoV-2-specific T-cell receptors (TCRs). The primary outcome was a comparison of anti-S IgG titers at the post-V2 time point in participants initiating vaccinations <4 months versus 4-12 months after HCT using a propensity-adjusted analysis. We also evaluated factors associated with high-level anti-S IgG titers (≥2403 U/mL) in logistic regression models. Findings: Between April 22, 2021 and November 17, 2021, 175 allogeneic HCT recipients were enrolled in the study, of whom all but one received mRNA SARS-CoV-2 vaccines. SARS-CoV-2 anti-S IgG titers, neutralizing antibody titers, and TCR breadth and depth did not significantly differ at all tested time points following the second vaccination among those initiating vaccinations <4 months versus 4-12 months after HCT. Anti-S IgG ≥2403 U/mL correlated with neutralizing antibody levels similar to those observed in a prior study of non-immunocompromised individuals, and 57% of participants achieved anti-S IgG ≥2403 U/mL at the end-of-study time point. In models adjusted for SARS-CoV-2 infection pre-enrollment, SARS-CoV-2 vaccination pre-HCT, CD19+ B-cell count, CD4+ T-cell count, and age (as applicable to the model), vaccine initiation timing was not associated with high-level anti-S IgG titers at the post-V2, post-V3, or end-of-study time points. Notably, prior graft-versus-host-disease (GVHD) or use of immunosuppressive medications were not associated with high-level anti-S IgG titers. Grade ≥3 vaccine-associated adverse events were infrequent. Interpretation: These data support starting mRNA SARS-CoV-2 vaccination three months after HCT, irrespective of concurrent GVHD or use of immunosuppressive medications. This is one of the largest prospective analyses of vaccination for any pathogen within the first year after allogeneic HCT and supports current guidelines for SARS-CoV-2 vaccination starting three months post-HCT. Additionally, there are few studies of mRNA vaccine formulations for other pathogens in HCT recipients, and these data provide encouraging proof-of-concept for the utility of early vaccination targeting additional pathogens with mRNA vaccine platforms. Funding: National Marrow Donor Program, Leukemia and Lymphoma Society, Multiple Myeloma Research Foundation, Novartis, LabCorp, American Society for Transplantation and Cellular Therapy, Adaptive Biotechnologies, and the National Institutes of Health.

MULTIMODAL IMAGING OF TWO UNCONVENTIONAL CASES OF BARTONELLA NEURORETINITIS.

PURPOSE: To report two cases of cat-scratch fever with atypical posterior segment manifestations. METHODS: Two cases were retrospectively reviewed. RESULTS: A 27-year-old woman presented with painless blurring of central vision in her left eye. Clinical examination revealed a small focal area of retinitis within the macula associated with a subtle macular star. Spectral-domain optical coherence tomography showed a hyper-reflective inner retinal lesion in addition to subretinal and intraretinal fluid as well as hyperreflective foci within the outer plexiform layer. Serology was positive for anti-B. henselae IgM (titer 1:32). A 34-year-old woman presented with painless loss of vision in both eyes associated with headaches and pain with extraocular movement. Spectral-domain optical coherence tomography depicted subretinal fluid, intraretinal fluid, and hyperreflective deposits within the outer plexiform layer. A focal collection of vitreous cell was observed overlying the optic nerve in the left eye. Bilateral disk leakage was identified on fluorescein angiography. Serology revealed high-titer anti-B. henselae antibodies (IgM titers 1:32, IgG titers 1:256). CONCLUSION: Our cases highlight the necessity of recognizing more unusual posterior segment presentations of ocular bartonellosis. Multimodal retinal imaging including spectral-domain optical coherence tomography may help better characterize lesions.

MULTIMODAL IMAGING OF PHOTIC MACULOPATHY FROM ARC WELDING.

PURPOSE: Photic retinal toxicity induced by exposure to arc welding can lead to irreversible vision loss. Serial multimodal imaging is characterized in a patient with outer retinal damage secondary to welder's maculopathy. METHODS: A single case was retrospectively reviewed. RESULTS: Spectral domain optical coherence tomography acutely revealed disruption of the ellipsoid zone, hyperreflective bands through the outer nuclear layer, and outer retinal cavitation consistent with phototoxicity. Subsequently, disruption and hypertrophy of the subfoveal retinal pigment epithelium developed. Autofluorescence depicted central hypoautofluorescence. CONCLUSION: We report serial multimodal imaging in welder's maculopathy to better characterize the evolution of lesions. Multimodal imaging including spectral domain optical coherence tomography in arc welding phototoxicity may share features with other forms of phototoxicity such as hand-held laser maculopathy.

Retinal injury from handheld lasers: a review.

Retinal photic injury induced by handheld lasers is a burgeoning public health concern due to the wider accessibility of high-powered devices. Retinal damage from thermal energy can cause potentially severe and permanent vision loss in children and young adults who are particularly vulnerable because of comorbid behavioral, learning, and psychiatric impairments. Understanding the spectrum of specific clinical and imaging features of such laser injuries aids in prompt and accurate diagnosis. Multimodal retinal imaging is important for the identification of the outer retinal abnormalities that characterize this condition. We reviewed 171 reported cases in the English and non-English language literature published from 1999, when handheld laser injury was first described, to December, 2018. Risk factors, demographic and clinical characteristics, as well as multimodal imaging findings, were collected and summarized. These findings both provide insights for public health awareness and guide areas of future investigation.

Comparative effectiveness and harms of intravitreal antivascular endothelial growth factor agents for three retinal conditions: a systematic review and meta-analysis.

Intravitreal antivascular endothelial growth factor (VEGF) agents are widely used to treat ocular conditions but the benefits and harms of these treatments are uncertain. We conducted a systematic review to compare the effects of aflibercept, bevacizumab and ranibizumab on best-corrected visual acuity (BCVA) changes, quality of life and ocular or systemic adverse events in patients with neovascular age-related macular degeneration (NVAMD), diabetic macular oedema (DME) and central or branch retinal vein occlusion (RVO). We searched published and unpublished literature sources to February 2017 for randomised controlled trials and cohort or modelling studies reporting comparative costs in the USA. Two reviewers extracted data and graded the strength of the evidence using established methods. Of 17 included trials, none reported a clinically important difference (≥ 5 letters) in visual acuity gains between agents. Nine trials provide high-strength evidence of no difference between bevacizumab and ranibizumab for NVAMD. Three trials provide moderate-strength evidence of no difference between bevacizumab and ranibizumab for DME. There was low-strength evidence of similar effects between aflibercept and ranibizumab for NVAMD, aflibercept and bevacizumab for RVO and all three agents for DME. There was insufficient evidence to compare bevacizumab and ranibizumab for RVO. Rates of ocular adverse events were low, and systemic harms were generally similar between groups, although 1 DME trial reported more arterial thrombotic events with ranibizumab versus aflibercept. Overall, no agent had a clear advantage over another for effectiveness or safety. Aflibercept and ranibizumab were significantly less cost-effective than repackaged bevacizumab in two trials. Systematic review registration number: CRD42016034076.

Quantitative Evaluation of Choroidal Neovascularization under Pro Re Nata Anti-Vascular Endothelial Growth Factor Therapy with OCT Angiography.

PURPOSE: To use optical coherence tomography angiography (OCTA) derived quantitative metrics to assess the response of choroidal neovascularization to pro-re-nata (PRN) anti-endothelial growth factor (anti-VEGF) treatment in neovascular age-related macular degeneration (AMD). DESIGN: Prospective longitudinal cohort study. PARTICIPANTS: Fourteen eyes from 14 study participants with treatment-naïve neovascular AMD were enrolled. METHODS: Subjects were evaluated monthly and treated with intravitreal anti-VEGF agents under a PRN protocol for one year. At each visit, two 3×3 mm2 OCTA scans were obtained. Custom image processing was applied to segment the outer retinal slab, suppress projection artifact, and automatically detect CNV. CNV membrane area (mm2) and CNV vessel area (mm2) was calculated. MAIN OUTCOMES: Individual and mean CNV membrane area and CNV vessel area at each visit; within-visit repeatability determined by coefficient of variation. RESULTS: Eight eyes had entire CNV within 3×3 mm2 scanning area and had adequate image quality for CNV quantification. One case (case #2) was excluded from analysis due to the presence of a large subretinal hemorrhage overlying the CNV membrane. In the remaining cases, CNV vessel area was reduced by 39%, 50%, 43%, and 41% at months 1, 3, 6, and 12 respectively. CNV membrane area was reduced by 39%, 51%, 54%, and 45% at months 1, 3, 6, and 12. At month 6, mean change from baseline was not statistically significant for CNV vessel area, while it was statistically significant for CNV membrane area. Neither metric was significantly different compared to baseline at month 12. Individual analyses revealed each CNV had a unique response under PRN treatment. Within-visit repeatability was was 7.96% (coefficient of variation) for CNV vessel area and 7.37% for CNV membrane area. CONCLUSIONS: In this small exploratory study of CNV response to PRN anti-VEGF treatment, both CNV vessel area and membrane area were reduced compared to baseline after three months. After one year of follow-up, these reductions were no longer statistically significant. When anti-VEGF treatment was held, increasing CNV vessel area over time often resulted in exudation, but it was not possible to exactly when exudation occurs.

Projection-resolved optical coherence tomography angiography exhibiting early flow prior to clinically observed retinal angiomatous proliferation.

PURPOSE: The purpose of this study is to analyze early retinal angiomatous proliferation (RAP) utilizing a novel imaging modality, Projection-Resolved Optical Coherence Tomography Angiography (PR-OCTA). OBSERVATIONS: Five months prior to the diagnosis of a RAP lesion, cross-sectional PR-OCTA demonstrated flow in the outer retina contiguous with the deep retinal capillary plexus (DCP) and adjacent to a small pigment epithelial detachment. After development of a clinically visible RAP lesion, cross-sectional PR-OCTA demonstrated the RAP lesion connecting DCP and sub-retinal pigment epithelial neovascularization. CONCLUSIONS & IMPORTANCE: This is the first report of PR-OCTA demonstrating abnormal flow in the outer retina prior to the development of a clinically detectable RAP lesion. PR-OCTA may be useful for surveillance and to help further characterize and stage RAP lesions.

Tractional Abnormalities of the Central Foveal Bouquet in Epiretinal Membranes: Clinical Spectrum and Pathophysiological Perspectives.

PURPOSE: To investigate the tractional alterations of the central bouquet (CB) in idiopathic epiretinal membranes (ERMs). DESIGN: Retrospective, consecutive, observational case series. METHODS: ERMs were classified according to a 4-stage grading system. The CB was defined as a circular area of approximately 100 µm composed of densely packed cones (and Müller cells) in the central fovea. Tractional abnormalities of the CB were identified with spectral-domain optical coherence tomography. Ex vivo histopathologic analysis was performed. RESULTS: In this study 263 eyes with ERMs were included. Mean follow-up was 21.2 ± 16.7 months. At baseline, tractional abnormalities of the CB were diagnosed in 58 out of 263 eyes (22%) and divided into 3 categories: cotton ball sign (defined as a fuzzy hyperreflective area between the ellipsoid zone and the interdigitation zone in the central fovea), foveolar detachment, and acquired vitelliform lesion. The presence of ectopic inner foveal layers was negatively correlated with the presence of CB tractional abnormalities (P = .002). Visual acuity was highest in association with the cotton ball sign and lowest in the acquired vitelliform lesion group. Sequential morphologic progression was identified in 7 eyes. Ex vivo histopathologic analysis illustrated characteristic staining patterns supporting a potential mechanism of traction by Müller cells in the CB. CONCLUSIONS: The cotton ball sign, foveolar detachment, and acquired vitelliform lesion may comprise a continuum in the same clinical spectrum and may represent subsequent stages of CB abnormalities. Foveal Müller cells may play an integral role in the transmission of mechanical forces to the central foveal cones.

Sensitivity and Specificity of OCT Angiography to Detect Choroidal Neovascularization.

PURPOSE: To determine the sensitivity and specificity of optical coherence tomography angiography (OCTA) in the detection of choroidal neovascularization (CNV) in age-related macular degeneration (AMD). DESIGN: Prospective case series. SUBJECTS: Prospective series of seventy-two eyes were studied, which included eyes with treatment-naive CNV due to AMD, non-neovascular AMD, and normal controls. METHODS: All eyes underwent OCTA with a spectral domain (SD) OCT (Optovue, Inc.). The 3D angiogram was segmented into separate en face views including the inner retinal angiogram, outer retinal angiogram, and choriocapillaris angiogram. Detection of abnormal flow in the outer retina served as candidate CNV with OCTA. Masked graders reviewed structural OCT alone, en face OCTA alone, and en face OCTA combined with cross-sectional OCTA for the presence of CNV. MAIN OUTCOME MEASURE: The sensitivity and specificity of CNV detection compared to the gold standard of fluorescein angiography (FA) and OCT was determined for structural SD-OCT alone, en face OCTA alone, and with en face OCTA combined with cross-sectional OCTA. RESULTS: Of 32 eyes with CNV, both graders identified 26 true positives with en face OCTA alone, resulting in a sensitivity of 81.3%. Four of the 6 false negatives had large subretinal hemorrhage (SRH) and sensitivity improved to 94% for both graders if eyes with SRH were excluded. The addition of cross-sectional OCTA along with en face OCTA improved the sensitivity to 100% for both graders. Structural OCT alone also had a sensitivity of 100%. The specificity of en face OCTA alone was 92.5% for grader A and 97.5% for grader B. The specificity of structural OCT alone was 97.5% for grader A and 85% for grader B. Cross-sectional OCTA combined with en face OCTA had a specificity of 97.5% for grader A and 100% for grader B. CONCLUSIONS: Sensitivity and specificity for CNV detection with en face OCTA combined with cross-sectional OCTA approaches that of the gold standard of FA with OCT, and it is better than en face OCTA alone. Structural OCT alone has excellent sensitivity for CNV detection. False positives from structural OCT can be mitigated with the addition of flow information with OCTA.

Acute macular neuroretinopathy: A comprehensive review of the literature.

Acute macular neuroretinopathy is a relatively rare condition originally defined by the presence of intraretinal, reddish-brown, wedge-shaped lesions, the apices of which tend to point toward the fovea. Acute onset of paracentral scotomas corresponding to the clinically evident lesions is both common and characteristic. Although the pathogenesis of acute macular neuroretinopathy is complex, recent research suggests a microvascular etiology. Advances in multimodal imaging have enabled better characterization of this retinal disorder and have led to newly proposed diagnostic criteria. We review 101 reported cases in the English and non-English language literature identified from 1975, when acute macular neuroretinopathy was first described, to December, 2014. We discuss common risk factors, demographic and clinical characteristics, and multimodal imaging findings, which together provide insights into pathogenesis and guide areas of future investigation.

Laser-Induced Photic Injury Phenocopies Macular Dystrophy.

OBJECTIVE: To describe the phenotypes associated with laser-induced retinal damage in children. METHODS: Five patients with maculopathy and reduced visual acuity associated with laser pointer use were evaluated. Best-corrected visual acuity, retinal structure, and function were monitored with color fundus, infrared (IR), and red-free images, fundus autofluorescence (AF), spectral domain-optical coherence tomography (SD-OCT), and full-field electroretinography (ERG). RESULTS: All five laser pointer injury patients had retinal lesions resembling a macular dystrophy (one bilateral and four unilateral). These lesions were irregular in shape but all had a characteristic dendritic appearance with linear streaks radiating from the lesion. Photoreceptor damage was present in all patients, but serial OCT monitoring showed that subsequent photoreceptor recovery occurred over time in the eyes of at least four patients. One patient also had bilateral pigment epithelial detachments (PED). Both hyper- and hypoautofluorecence were observed in the laser damage area. CONCLUSIONS: In general, OCT and IR images are quite useful to diagnose laser damage, but AF is not as sensitive. Laser pointer damage in children can occasionally be misdiagnosed as a macular dystrophy disease, but the distinctive lesions and OCT features are helpful for differentiating laser damage from other conditions.

Visualization of 3 Distinct Retinal Plexuses by Projection-Resolved Optical Coherence Tomography Angiography in Diabetic Retinopathy.

IMPORTANCE: Projection artifacts in optical coherence tomography angiography (OCTA) blur the retinal vascular plexuses together and limit visualization of the individual plexuses. OBJECTIVE: To describe projection-resolved (PR) OCTA in eyes with diabetic retinopathy (DR) and healthy eyes. DESIGN, SETTING, AND PARTICIPANTS: In this case-control study, patients with DR and healthy controls were enrolled in this observational study from January 26, 2015, to December 4, 2015, at a tertiary academic center. Spectral-domain, 70-kHz OCT obtained 3 × 3-mm macular scans. The PR algorithm suppressed projection artifacts. A semiautomated segmentation algorithm divided PR-OCTA into superficial, intermediate, and deep retinal plexuses. Two masked graders examined 3-layer PR-OCTA and combined angiograms for nonperfusion and abnormal capillaries. MAIN OUTCOMES AND MEASURES: Retinal nonperfusion and capillary abnormalities and the diagnostic accuracy of detecting DR. RESULTS: Twenty-nine eyes of 15 healthy individuals (mean [SD] age, 36.2 [13.4] years; 11 women) and 47 eyes of 29 patients with DR (mean [SD] age, 55.5 [11.9]; 10 women) underwent imaging. PR-OCTA revealed 3 distinct retinal plexuses in their known anatomical locations in all eyes. The intermediate and deep plexuses of healthy eyes revealed capillary networks of uniform density and caliber, whereas the superficial plexus revealed vessels in the familiar centripetal branching pattern. In eyes with DR, 3-layer PR-OCTA disclosed incongruent areas of nonperfusion and varied vessel caliber and density in the deeper plexuses. Masked grading of capillary nonperfusion on 3-layer PR-OCTA detected DR with 100% sensitivity (95% CI, 90.8%-100%) and 100% specificity (95% CI, 85.4%-100%). With unsegmented retinal angiograms, the sensitivity and specificity were 78.7% (95% CI, 63.9%-88.8%) and 100% (95% CI, 85.4%-100%), respectively (P = .002 for sensitivity). On 3-layer PR-OCTA, sensitivity was 72.2% (95% CI, 54.6%-85.2%) for severe nonproliferative DR and proliferative DR eyes with generalized nonperfusion in 2 or more individual plexuses, but on combined angiogram, sensitivity was 25.0% (95% CI, 12.7%-42.5%) for generalized nonperfusion (P < .001). PR-OCTA disclosed dilated vessels in the intermediate and deep plexuses in 23 eyes (100%) with proliferative DR, 13 eyes (100%) with severe nonproliferative DR, 8 eyes (73%) with mild to moderate nonproliferative DR, and 0 control eyes. CONCLUSIONS AND RELEVANCE: By presenting 3 retinal vascular plexuses distinctly, PR-OCTA reveals capillary abnormalities in deeper layers with clarity and may distinguish DR from healthy eyes and severe DR from mild DR with greater accuracy compared with conventional OCTA.