Synthesis and preliminary evaluation of novel PET probes for GSK-3 imaging.

Non-invasive imaging of GSK-3 expression in the brain will help to understand the role of GSK-3 in disease pathology and progression. Herein, we report the radiosynthesis and evaluation of two novel isonicotinamide based 18F labeled PET probes, [18F]2 and [18F]6 for noninvasive imaging of GSK3. Among the developed PET probes, the in vitro blood-brain permeability coefficient of 2 (38 ± 20 × 10-6 cm/s, n = 3) was found to be better than 6 (8.75 ± 3.90 × 10-6 cm/s, n = 5). The reference compounds 2 and 6 showed nanomolar affinity towards GSK-3α and GSK-3ß. PET probe [18F]2 showed higher stability (100%) in mouse and human serums compared to [18F]6 (67.01 ± 4.93%, n = 3) in mouse serum and 66.20 ± 6.38%, n = 3) in human serum at 120 min post incubation. The in vivo imaging and blocking studies were performed in wild-type mice only with [18F]2 due to its observed stability. [18F]2 showed a SUV of 0.92 ± 0.28 (n = 6) in mice brain as early as 5 min post-injection followed by gradual clearance over time.

Optical coherence tomography homography for detection of retinal displacement: a validation study.

PURPOSE: Retinal displacement following rhegmatogenous retinal detachment (RRD) has been associated with inferior functional outcomes. Recent evidence using an overlay technique suggests that fundus-autofluorescence underestimates post-RRD repair retinal displacement. This study aims to validate the overlay technique in normal eyes and to determine its sensitivity and specificity at detecting retinal displacement. METHODS: We conducted a retrospective case series involving 66 normal eyes, each with at least two separate infrared (IR) images at different time points. Overlay of the two images was based on manual marking of choroidal and optic nerve head (ONH) landmarks. For each set of two IR images, computer code for homography generated two outputs, flipping view video and an overlay picture. First, validation of choroidal/ONH alignment was performed using the flipping view video to ensure accurate manual markings. Then, two different masked graders (AB + IM) evaluated the overlays for presence of retinal displacement. 16 control eyes following RRD repair with detected retinal displacement on FAF imaging assessed sensitivity and specificity of the technique. RESULTS: 94% of overlays were found to be well aligned (62/66). 11 cases exhibited errors on flipping view analysis (choroidal/ONH misalignment). Those 11 cases had a significantly higher rate of retinal displacement (false positives) compared to cases without errors (8/11,72% Vs 54/55,98%,P = 0.001). Sensitivity and specificity of the overlay technique for detecting retinal displacement considering only adequate flipping view cases (n = 55) were calculated as 100% and 98%, respectively. CONCLUSIONS: IR overlay emerges as a reliable and valid method for detecting retinal displacement, exhibiting excellent sensitivity and specificity.

Optical Coherence Tomography Features in Fovea-Off Exudative vs Rhegmatogenous Retinal Detachment.

PURPOSE: To describe the optical coherence tomography (OCT) features that can differentiate eyes with fovea-off exudative retinal detachment (ERD) vs. rhegmatogenous retinal detachment (RRD), with particular attention to outer retinal corrugations (ORCs). DESIGN: Multicenter, retrospective cross-sectional study. METHODS: Multicenter, retrospective cross-sectional study of patients diagnosed with unilateral or bilateral fovea-off ERD or primary, acute, fovea-off RRD between 2016 and 2021. This study was performed with the approval from the Research Ethics Board at the University of Toronto and was conducted in accordance with the Declaration of Helsinki. Patients with any ERD etiology and evidence of extensive, bullous fovea-off detachment and in the RRD group: consecutive patients with acute, primary fovea-off RRD with good quality baseline SD-OCT imaging were included. Patients with exudative choroidal neovascularization from any etiology, optic nerve pit, significant media opacity, or OCT images with poor quality or low signal strength were excluded. Primary outcome was to describe the morphological features of the macula using SD-OCT in patients diagnosed with ERD vs RRD, with specific interest in ORCs. RESULTS: 161 eyes (51 ERD and 110 RRD) of 154 patients were included. Fifty-one eyes with ERD presented with 1 of 15 etiologies. ERD were associated with a greater risk of having hyperreflective dots in the outer retina (92.2% vs 74.5%, p=0.009), hyperreflective material and dots in the subretinal fluid (72.5% vs 34.5%, p<0.001), internal limiting membrane and inner retinal undulations (70.6% vs 39.4%, p<0.001), and retinal pigment epithelium undulations (44.9% vs 6.4%, p<0.001) compared to RRD. RRD was associated with a greater risk of outer retinal corrugations (80% vs 0%, p<0.001), intraretinal fluid (90.9% vs 41.2%, p<0.001) and ellipsoid zone thickening (90% vs 66.7%, p<0.001) compared to ERD. CONCLUSION: The presence of ORCs are highly specific for RRD and absent in ERD. This is likely related to differences in the pathophysiology of the diseases process, specifically the content of the subretinal fluid. Understanding the differences in OCT morphological features of ERD vs RRD may aid with diagnosis and management.

Daptomycin-Induced Eosinophilic Pneumonia: Can an Antibiotic Cause Pneumonia?

We present an interesting case of a patient who was discharged from the hospital on daptomycin and ertapenem in the setting of osteomyelitis. The patient did not have any respiratory symptoms during that hospital stay. A few weeks after discharge, the patient came back to the hospital with complaints of fever and shortness of breath. Chest X-ray showed pulmonary infiltrates. Initially, the patient was treated for acute respiratory distress syndrome (ARDS) vs pneumonia, but she did not improve. When labs showed significant eosinophilia, daptomycin-induced eosinophilic pneumonia became the working diagnosis, and the patient improved significantly when daptomycin was discontinued and steroids were started.

Emergent decommissioning of HeartMate 3 for life-threatening hemorrhage.

Left ventricular assist devices are known for the treatment of heart failure. We present a patient who underwent emergent decommissioning of his left ventricular assist device after experiencing life-threatening hemorrhage. In this case, the patient's outflow graft was avulsed from his left subclavian artery. We used a covered stent to first exclude the outflow graft and an Amplatzer II plug (Abbott Cardiovascular) to then occlude the inflow cannula. Accessing the inflow cannula of the left ventricular assist device was challenging. In hindsight, we could have accessed and occluded the outflow graft via the left subclavian artery before deploying the covered stent.

Two-year outcomes of different subretinal fluid drainage techniques during vitrectomy for fovea-off rhegmatogenous retinal detachments: ELLIPSOID-2 Study.

BACKGROUND: The purpose of the study is to compare visual acuity, complications and outer retinal integrity following subretinal fluid (SRF) drainage from the peripheral retinal breaks (PRBs) versus posterior retinotomy (PR) versus perfluorocarbon liquid (PFCL) for macula-off rhegmatogenous retinal detachments (RRDs) at 2 years post-surgery. METHODS: Retrospective analysis of 300 consecutive patients with primary RRD undergoing 23-gauge pars plana vitrectomy with SRF drainage through (1) PRB (n=100), (2) PR (n=100) or (3) with PFCL (n=100). Primary outcomes were visual acuity (best-corrected visual acuity (BCVA)) and complications (cystoid macular oedema (CMO) and epiretinal membrane (ERM)). Secondary outcomes were discontinuity of the external limiting membrane (ELM), ellipsoid zone (EZ) and interdigitation zone (IDZ) at 2 years post-surgery. RESULTS: Mean (±SD) logMAR BCVA at 24 months was better in the PRB compared with PR and PFCL, with PFCL having the worst BCVA (PRB 0.5±0.6; PR 0.7±0.5; PFCL 0.9±0.7, p=0.001). CMO was higher with PFCL (PRB 29.7%; PR 30.2%; PFCL 45.9%, p=0.0015) and ERM formation was higher in PR (PRB 62.6%; PR 93.0%; PFCL 68.9%, p=0.002). There were no differences in ELM or EZ discontinuity. However, IDZ discontinuity was higher in PFCL (PRB 34%; PR 27%; PFCL 46%, p=0.002) at 2 years. CONCLUSIONS: Visual acuity was worse and discontinuity of the IDZ and CMO was greater in eyes with PFCL-assisted drainage compared with PRB or PR. Drainage technique may impact long-term visual acuity and photoreceptor integrity.

Impact of Baseline Morphologic Stage of Rhegmatogenous Retinal Detachment on Postoperative Visual Acuity.

PURPOSE: To evaluate the association of baseline morphologic stage of rhegmatogenous retinal detachment (RRD) using OCT with postoperative anatomic and visual acuity (VA) outcomes. DESIGN: Retrospective cohort study. SUBJECTS: Consecutive primary fovea-involving RRDs referred from January 2012 to September 2022. METHODS: Patients with primary RRD and no prior macular pathology with gradable baseline OCT were assessed. Best-corrected VA (BCVA) was assessed at presentation and at 3, 6, and 12 months postoperatively. OCT scans were graded for parafoveal morphologic stage of RRD and foveal photoreceptor integrity. MAIN OUTCOME MEASURES: Association of morphologic stage of RRD with 12-month BCVA. RESULTS: Three hundred fifty-one patients were included. Sixty-eight percent (238/351) were male, the mean (standard deviation) age was 61.2 (± 12.8) years, and 59% (206/351) were phakic. Thirteen percent (47/351) presented in stages 1 and 2, 15% (54/351) in stage 3a, 36% (126/351) in stage 3b, 24% (83/351) in stage 4, and 12% (41/351) in stage 5. Increasing stage was associated with worse foveal photoreceptor integrity, reduced baseline BCVA and longer duration of central vision loss (P < 0.001). Mean (standard deviation) 12-month BCVA by stage was 0.77 (± 0.64) for stages 1 and 2, 1.00 (± 0.53) for stage 3a, 1.36 (± 0.55) for stage 3b, 1.33 (± 0.66) for stage 4 and 1.55 (± 0.47) for stage 5. Increasing stage was associated with reduced postoperative BCVA (P < 0.001) at all time points after adjusting for covariates. A subgroup analysis of acute detachments with retinal pigment epithelium-photoreceptor dysregulation demonstrated no difference in postoperative BCVA between stages 1, 2, and 3a. However, 12-month BCVA was significantly better in stages 1, 2, and 3a vs. stage 3b (P = 0.002) and stage 3a vs. 3b (P = 0.008). CONCLUSIONS: This study validates the clinical relevance of a recently proposed OCT-based staging system for outer retinal morphologic changes over time in RRD. Postoperative BCVA was significantly reduced in patients with worse presenting stage at all time points. In acute RRDs, 12-month BCVA was significantly better in stages 1, 2, and 3a vs. stage 3b, which suggests early stages may have better retinal recovery compared with stage 3b or worse. Stage 3b may represent a critical point where substantial structural changes occur, leading to worse outcomes in acute RRDs. Patients presenting with fovea-involving RRDs in stages 1, 2, or 3a may benefit from more urgent intervention. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure: The ARIES-HM3 Randomized Clinical Trial.

IMPORTANCE: Left ventricular assist devices (LVADs) enhance quality and duration of life in advanced heart failure. The burden of nonsurgical bleeding events is a leading morbidity. Aspirin as an antiplatelet agent is mandated along with vitamin K antagonists (VKAs) with continuous-flow LVADs without conclusive evidence of efficacy and safety. OBJECTIVE: To determine whether excluding aspirin as part of the antithrombotic regimen with a fully magnetically levitated LVAD is safe and decreases bleeding. DESIGN, SETTING, and PARTICIPANTS: This international, randomized, double-blind, placebo-controlled study of aspirin (100 mg/d) vs placebo with VKA therapy in patients with advanced heart failure with an LVAD was conducted across 51 centers with expertise in treating patients with advanced heart failure across 9 countries. The randomized population included 628 patients with advanced heart failure implanted with a fully magnetically levitated LVAD (314 in the placebo group and 314 in the aspirin group), of whom 296 patients in the placebo group and 293 in the aspirin group were in the primary analysis population, which informed the primary end point analysis. The study enrolled patients from July 2020 to September 2022; median follow-up was 14 months. Intervention: Patients were randomized in a 1:1 ratio to receive aspirin (100 mg/d) or placebo in addition to an antithrombotic regimen. MAIN OUTCOMES AND MEASURES: The composite primary end point, assessed for noninferiority (-10% margin) of placebo, was survival free of a major nonsurgical (>14 days after implant) hemocompatibility-related adverse events (including stroke, pump thrombosis, major bleeding, or arterial peripheral thromboembolism) at 12 months. The principal secondary end point was nonsurgical bleeding events. RESULTS: Of the 589 analyzed patients, 77% were men; one-third were Black and 61% were White. More patients were alive and free of hemocompatibility events at 12 months in the placebo group (74%) vs those taking aspirin (68%). Noninferiority of placebo was demonstrated (absolute between-group difference, 6.0% improvement in event-free survival with placebo [lower 1-sided 97.5% CI, -1.6%]; P < .001). Aspirin avoidance was associated with reduced nonsurgical bleeding events (relative risk, 0.66 [95% confidence limit, 0.51-0.85]; P = .002) with no increase in stroke or other thromboembolic events, a finding consistent among diverse subgroups of patient characteristics. CONCLUSIONS AND RELEVANCE: In patients with advanced heart failure treated with a fully magnetically levitated LVAD, avoidance of aspirin as part of an antithrombotic regimen, which includes VKA, is not inferior to a regimen containing aspirin, does not increase thromboembolism risk, and is associated with a reduction in bleeding events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04069156.

Positron Emission Tomography Imaging of Cell Trafficking: A Method of Cell Radiolabeling.

Stem cell and chimeric antigen receptor (CAR) T-cell therapies are emerging as promising therapeutics for organ regeneration and as immunotherapy for various cancers. Despite significant progress having been made in these areas, there is still more to be learned to better understand the pharmacokinetics and pharmacodynamics of the administered therapeutic cells in the living system. For noninvasive, in vivo tracking of cells with positron emission tomography (PET), a novel [89Zr]Zr-p-isothiocyanatobenzyl-desferrioxamine ([89Zr]Zr-DBN)-mediated cell radiolabeling method has been developed utilizing 89Zr (t1/2 78.4 h). The present protocol describes a [89Zr]Zr-DBN-mediated, ready-to-use, radiolabeling synthon for direct radiolabeling of variety of cells, including mesenchymal stem cells, lineage-guided cardiopoietic stem cells, liver regenerating hepatocytes, white blood cells, melanoma cells, and dendritic cells. The developed methodology enables noninvasive PET imaging of cell trafficking for up to 7 days post-administration without affecting the nature or the function of the radiolabeled cells. Additionally, this protocol describes a stepwise method for the radiosynthesis of [89Zr]Zr-DBN, biocompatible formulation of [89Zr]Zr-DBN, preparation of cells for radiolabeling, and finally the radiolabeling of cells with [89Zr]Zr-DBN, including all the intricate details needed for the successful radiolabeling of cells.

Pathophysiology of Secondary Macular Hole in Rhegmatogenous Retinal Detachment.

Purpose: To describe the pathophysiology of secondary macular hole (MH) in rhegmatogenous retinal detachment (RRD). Methods: A retrospective cohort of 360 consecutive primary fovea-off RRDs presenting to St. Michael's Hospital, Toronto, from January 2012 to September 2022 were included. Preoperative OCT was assessed for bacillary layer detachment (BALAD) abnormalities. Histological sections of normal eyes were assessed to inform OCT interpretations. Primary outcome measure was the progression of BALAD to full-thickness MH (FTMH). Results: Of the 360 patients, 22.5% (n = 81) had BALAD abnormalities at presentation. Eight percent (29/360) had associated MH, of which 79.3% (23/29) were a BALAD-lamellar hole and 20.7% (6/29) were FTMH. After reattachment, 62% of MHs persisted (18/29), of which 83% (15/18) had BALAD-lamellar holes that subsequently progressed to FTMH in a mean of 8.1 ± 3.2 days. BALAD-lamellar holes had significantly worse postoperative visual acuity (P < 0.001) when compared with other BALAD abnormalities (58/81) or with the rest of the cohort (279/360). OCT spectrum from BALAD to FTMH includes (1) cleavage planes extending from Henle fiber layer into the BALAD; (2) central outer nuclear layer thinning; (3) Müller cell cone loss with tissue remnants at the foveal walls; (4) retinal tissue operculum close to BALAD-MH; and (5) progressive thinning or degradation of the posterior band of BALAD-lamellar hole leading to FTMH. Histological specimens identified foveal regions of low mechanical stability. Conclusions: BALAD plays a crucial role in the pathophysiology of MH in RRDs, which forms owing to sequential changes in four critical areas: RPE-photoreceptor interface, myoid zone, Henle fiber layer, and Müller cell cone with surrounding tissue. Timely management of fovea-off RRD with BALAD may be prudent to avoid the progression to BALAD-lamellar hole, subsequent FTMH, and worse functional outcomes.

In-Office Suprachoroidal Viscopexy for Rhegmatogenous Retinal Detachment Repair.

Importance: In-office suprachoroidal viscopexy (SCVEXY) is a minimally invasive technique for rhegmatogenous retinal detachment (RRD) repair that can be performed with no incision, no tamponade agent, and no positioning requirements. This technique has the potential to be a step forward in the armamentarium to treat RRDs. Objective: To describe in-office SCVEXY for RRD repair. Design, Setting, and Participant: In this single-case report with short follow-up, a man in his 50s with pseudophakia and recent visual loss presented to St Michael's Hospital, Unity Health Toronto, with a fovea-off RRD in the right eye, extending from 6 to 10 o'clock, with no visible causative retinal break. Exposure: Injection of suprachoroidal sodium hyaluronate, 1%, in the region of the suspected break, using a 30-gauge needle with a custom-made guard that exposed only 1 mm of the needle. Main Outcome and Measures: Ability to perform in-office SCVEXY and to obtain a visible choroidal indentation. Results: After the procedure, a dome-shaped choroidal convexity was present in the superior temporal area. The patient achieved macular reattachment in less than 24 hours with no postoperative abnormalities, such as outer retinal folds, residual subfoveal fluid, or retinal displacement, with rapid recovery of the outer retinal bands on optical coherence tomography. The optical coherence tomography scans acquired in the area of the choroidal convexity demonstrated the location of the viscoelastic material in the suprachoroidal space. Laser retinopexy was applied in the suspected region of the retinal tear, and the patient was able to resume normal activity immediately after the procedure with no restrictions. Conclusions and Relevance: Suprachoroidal viscopexy is feasible as an in-office technique to create a temporary choroidal buckle for RRD repair. It is a minimally invasive procedure with the potential to maximize anatomical outcomes of integrity and postoperative functional outcomes in RRD because its mechanism of action does not require drainage of subretinal fluid or intraocular gas tamponade. Nevertheless, this was a single-case report with short follow-up, which limits the ability to determine the procedure's benefits, potential adverse events, failure rates, and best-case selection. Further work is required to refine the procedure and assess its efficacy and safety.

Retinal Displacement after Scleral Buckle versus Combined Buckle and Vitrectomy for Rhegmatogenous Retinal Detachment: ALIGN Scleral Buckle versus Pars Plana Vitrectomy with Scleral Buckle.

PURPOSE: To assess the risk of retinal displacement after scleral buckle (SB) versus pars plana vitrectomy with SB (PPV-SB). DESIGN: Multicenter prospective nonrandomized clinical trial. METHODS: The study took place at VitreoRetinal Surgery in Minneapolis, Minnesota, Sankara Nethralaya in Chennai, India, and St. Michael's Hospital in Toronto, Canada from July 2019 to February 2022. Patients who underwent successful SB or PPV-SB for fovea-involving rhegmatogenous retinal detachment with gradable postoperative fundus autofluorescence (FAF) imaging were included in the final analysis. Two masked graders assessed FAF images 3 months postoperatively. Metamorphopsia and aniseikonia were assessed with M-CHARTs and the New Aniseikonia Test, respectively. The primary outcome was the proportion of patients with retinal displacement detected with retinal vessel printings on FAF in SB versus PPV-SB. RESULTS: Ninety-one eyes were included in this study, of which 46.2% (42 of 91) had SB and 53.8% (49 of 91) underwent PPV-SB. Three months postoperatively, 16.7% (7 of 42) in the SB group and 38.8% (19 of 49) in the PPV-SB group had evidence of retinal displacement (difference = 22.1%; odds ratio = 3.2; 95% confidence interval [CI], 1.2-8.6; P = 0.02) on FAF. The statistical significance of this association increased after adjustment for extent of retinal detachment, baseline logarithm of the minimum angle of resolution, lens status, and sex in a multivariate regression analysis (P = 0.01). Retinal displacement was detected in 22.5% (6 of 27) of patients in the SB group with external subretinal fluid drainage and 6.7% (1 of 15) of patients without external drainage (difference = 15.8%; odds ratio = 4.0; 95% CI, 0.4-36.9; P = 0.19). Mean vertical metamorphopsia, horizontal metamorphopsia (MH), and aniseikonia were similar between patients in the SB and PPV-SB groups. There was a trend to worse MH in patients with retinal displacement versus those without retinal displacement (P = 0.067). CONCLUSIONS: Scleral buckle is associated with less retinal displacement compared with PPV-SB, indicating that traditional PPV techniques cause retinal displacement. There is a trend toward increased risk of retinal displacement in SB eyes that underwent external drainage compared with SB eyes without drainage, which is consistent with our understanding that the iatrogenic movement of subretinal fluid, such as that which occurs intraoperatively during external drainage with SB, may induce retinal stretch and displacement if the retina is then fixed in the stretched position. There was a trend to worse MH at 3 months in patients with retinal displacement. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Fluid-Fluid Exchange and External Needle Drainage with Minimal Gas Vitrectomy Associated with Retinal Displacement.

PURPOSE: To determine if fluid-fluid exchange (endo-drainage) or external needle drainage can result in retinal displacement following minimal gas vitrectomy (MGV) with no fluid-air exchange for rhegmatogenous retinal detachment (RRD) repair. METHODS: Two patients with macula off RRD underwent MGV with and without segmental buckle. First case had minimal gas vitrectomy with segmental buckle (MGV-SB), along with endo-drainage, while the second case had MGV only with external fluid drainage. At the completion of surgery, the patient was immediately log rolled to face down for 6 hours followed by positioning to the break. RESULTS: Both patients achieved retinal reattachment and post-operative wide-field fundus autofluorescence imaging demonstrated a low integrity retinal attachment (LIRA) with retinal displacement. CONCLUSIONS: Iatrogenic fluid drainage techniques such as fluid-fluid exchange or external needle drainage during MGV (without fluid-air exchange) may result in retinal displacement. Allowing the retinal pigment epithelial pump to reabsorb the fluid naturally may reduce the risk of retinal displacement.

Pathophysiology of outer retinal corrugations: Imaging dataset and mechanical models.

This article presents high-resolution swept-source optical coherence tomography (SS-OCT) imaging data used to elaborate a mechanical model that elucidates the formation of outer retinal corrugations (ORCs) in rhegmatogenous retinal detachments (RRD). The imaging data shared in the repository and presented in this article is related to the research paper entitled "Outer Retinal Corrugations in Rhegmatogenous Retinal Detachment: The Retinal Pigment Epithelium-Photoreceptor Dysregulation Theory" (Muni et al., AJO, 2022). The dataset consists of 69 baseline cross-sectional SS-OCT scans from 66 patients that were assessed for the presence of ORCs and analyzed considering the clinical features of each case. From the 66 cases, we selected SS-OCT images of 4 RRD patients with visible ORCs and no cystoid macular edema (CME) to validate the mechanical model. We modelled the retina as a composite material consisting of the outer retinal layer (photoreceptor layer) and the inner retinal layer (the part of the retina that excludes the photoreceptor layer) with thicknesses T o and T i and elastic modulus E o and E i , respectively. The thickness of the outer and inner retinal layers and the relative increase in the length of the outer retinal layer (γ) were measured from the SS-OCT images. Measurements from the SS-OCT images of patients with RRD demonstrated a 30% increase (γ=0.3) in the length of the outer retinal layer and a 400% increase in the thickness of the outer retinal layer (To). Using the mathematical model, Eo/Ei ranged between 0.05 to 0.5 to result in ORCs with a similar frequency to those observed in the SS-OCT scans.

En Face OCT in Diagnosis of Persistent Subretinal Fluid and Outer Retinal Folds after Rhegmatogenous Retinal Detachment Repair.

PURPOSE: To evaluate the role of en face OCT as a diagnostic tool for the detection of persistent subretinal fluid (PSRF) and outer retinal folds (ORFs) after successful rhegmatogenous retinal detachment (RRD) repair. DESIGN: Observational post hoc analysis of 2 prospective surgical trials. PARTICIPANTS: All patients with gradable (signal strength ≥ 5 and no segmentation error) 6 × 6-mm2 macular cube scans obtained using spectral-domain OCT (Carl Zeiss Meditec) between 1 and 2 months after surgery were included in this study. METHODS: The scans were assessed for the presence or absence of PSRF or ORFs using en face OCT and cross-sectional B scans by 2 masked graders, with any disagreements adjudicated by a third senior masked grader. MAIN OUTCOME MEASURES: The sensitivity, specificity, and predictive accuracy (using area under the curve [AUC]) of en face OCT were compared with those of cross-sectional OCT, which is considered the gold standard. RESULTS: Two hundred twenty-three patients were included in this study. The Cohen kappa between the graders in the diagnosis of PSRF and ORFs using en face OCT was 0.84 and 0.86, respectively. The sensitivity of en face OCT was 100% (95% confidence interval [CI], 100%-100%) in the diagnosis of PSRF and 98.8% (95% CI, 96.5%-101.1%) in the diagnosis of ORFs. Similarly, the specificity of en face OCT was 98.7% (95% CI, 96.8%-100.5%) and 84.2% (95% CI, 78.1%-90.2%) in the diagnosis of PSRF and ORFs, respectively. The AUC was 0.99 for PSRF and 0.91 for ORFs. CONCLUSIONS: En face OCT has good sensitivity, specificity, and predictive accuracy (using AUC) in the diagnosis of PSRF and ORFs. En face OCT is an efficient screening tool for postoperative anatomic abnormalities, such as PSRF and ORFs, after RRD repair. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

BACILLARY LAYER DETACHMENT AND ASSOCIATED ABNORMALITIES IN RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To describe bacillary layer detachment and related abnormalities of the foveal bouquet in rhegmatogenous retinal detachment and assess their impact on photoreceptor recovery and full-thickness macular hole formation, using optical coherence tomography. METHODS: Prospective cohort of 93 consecutive patients with fovea-off rhegmatogenous retinal detachment presenting to St. Michael's Hospital from January 2020 to April 2022, with gradable preoperative foveal optical coherence tomography. RESULTS: 23.7% (22/93) of patients had evidence of bacillary layer detachment and associated abnormalities. The mean fovea-off duration was 6.4 days (±5.6 SD). 86.4% (19/22) had foveal bacillary layer detachment, 15.8% (3/19) of which had cleavage planes extending from the outer nuclear layer into the myoid zone, and 14% (3/22) had an inner lamellar hole with a residual bridge of photoreceptor remnants (all of which progressed to full-thickness macular hole). Among patients with gradable optical coherence tomography at 3 months post-operatively, 80% (12/15) had ellipsoid zone discontinuity, which persisted in 41% (5/12) at 1 year. CONCLUSION: Bacillary layer detachment was described for the first time in the setting of rhegmatogenous retinal detachment. This is hypothesized to occur from horizontal traction secondary to hydration/lateral expansion of the outer retina in the presence of the Müller cell cone scaffold. Bacillary layer detachment may render the fovea susceptible to further injury, possibly representing a pathophysiological basis for full-thickness macular hole formation in rhegmatogenous retinal detachment.

Persistent subfoveal fluid in pneumatic retinopexy versus pars plana vitrectomy for rhegmatogenous retinal detachment: posthoc analysis of the PIVOT randomised trial.

PURPOSE: To assess the incidence of persistent subfoveal fluid (PSFF) in pneumatic retinopexy (PnR) versus pars plana vitrectomy (PPV) following rhegmatogenous retinal detachment (RRD) repair and to determine its association with functional outcomes. METHODS: Posthoc analysis of the PIVOT randomised trial. Eyes with gradable en face and cross-sectional spectral-domain optical coherence tomography (SD-OCT) scans at 1-2 months postoperatively were included. Primary outcome was the proportion of patients with PSFF following PnR versus PPV at 1-2 months postoperatively. Secondary outcomes included association of PSFF with Early Treatment Diabetic Retinopathy Study (ETDRS) letter score at 3, 6 and 12 months and metamorphopsia score (MCHARTs) at 12 months. RESULTS: Of 176 participants enrolled in PIVOT, 158 (89.8%) had gradable SD-OCT scans. Intergrader agreement was 0.870 (Cohen's kappa). The incidence of PSFF was 16% (13/81) following PnR and 10.4% (8/77) following PPV (p=0.298; OR=1.65, 95% CI 0.64 to 4.23). Median ETDRS score at 3 months postoperatively between eyes with and without PSFF was 71 (IQR=58-78) and 78 (IQR=70-84), respectively (difference=7 letters, p=0.037), with no significant difference at subsequent 6-month and 12-month visits. Median metamorphopsia scores in patients with versus without PSFF were: horizontal: 0.1 (IQR=0-0.3) vs 0 (IQR=0-0.2) (difference=0.1, p=0.228) and vertical: 0.25 (IQR=0-0.4) vs 0 (IQR=0-0.2) (difference=0.25, p=0.148), respectively. CONCLUSIONS: There was no significant difference in the incidence of PSFF in eyes undergoing PnR versus PPV for RRD. The presence of PSFF at 1-2 months postoperatively was associated with worse ETDRS letter score at 3 months, but there was no difference at 1 year. TRIAL REGISTRATION NUMBER: NCT01639209.

Outer Retinal Corrugations in Rhegmatogenous Retinal Detachment: The Retinal Pigment Epithelium-Photoreceptor Dysregulation Theory.

PURPOSE: Outer retinal folds occur when outer retinal corrugations (ORCs) persist after retinal reattachment with worse functional outcomes. We investigate the pathophysiology of ORCs in vivo. DESIGN: Prospective cohort study. METHODS: Patients with rhegmatogenous retinal detachment (RRD) presenting to St. Michael's Hospital, Toronto, Ontario, Canada, between August 2020 and February 2022 were assessed with swept-source optical coherence tomography (SS-OCT) and ultra-widefield SS-OCT for ORCs. Clinical characteristics of eyes with/without ORCs were compared. Mathematical models were used to deduce mechanical properties leading to ORCs. RESULTS: Sixty-six patients were included. More than half (60.6%, 40/66) were fovea-off and 48.4% (32/66) had ORCs at presentation. All eyes (32/32) with ORCs had retinal pigment epithelium (RPE)-photoreceptor dysregulation for at least 2 days, defined as loss of RPE control with acute, progressive, and extensive RRDs. In all (34/34) eyes without ORCs the RPE was in relative control of the subretinal space with nonprogressive subclinical or small localized or resolving RRDs, or with RPE-photoreceptor dysregulation for fewer than 2 days. Mathematical models indicate that a modulus of elasticity of the outer retina relative to the inner retina of 0.05 to 0.5 leads to ORCs. CONCLUSIONS: ORCs develop with (1) acute exposure of subretinal space to liquified vitreous, (2) for >2 days, that (3) overwhelms RPE capacity, leading to progressive and extensive RRD. Mathematical models suggest that a reduction in the modulus of elasticity of the outer retina occurs such that intrinsic compressive forces, likely related to progressive outer retinal hydration and lateral expansion, lead to ORCs. Understanding the pathophysiology of ORCs has implications for management.