Novel classification system for management of rhegmatogenous retinal detachment with minimally invasive detachment surgery: a network meta-analysis of randomized trials focused on patient-centred outcomes.

OBJECTIVE: To describe a novel classification system for primary rhegmatogenous retinal detachment (RRD) based on level 1 evidence assessing the functional outcomes of repair techniques with the goal of using a minimally invasive detachment surgery. METHODS: A systematic review and network meta-analysis of randomized, controlled trials comparing pneumatic retinopexy (PnR), scleral buckle (SB), or pars plana vitrectomy (PPV) for RRD was conducted. Primary outcomes were best-corrected visual acuity (BCVA), metamorphopsia, and operative complications. A meta-analysis was performed with a random effects maximum likelihood model, with outcomes of standardized mean difference (SMD) or risk ratio (RR) and 95% confidence interval. Inclusion and exclusion criteria were assessed to inform a classification system. RESULTS: Fourteen trials were included. RRDs were classified from categories 1-3 based on configuration (simple to complex). There was no significant difference in final BCVA between PnR and PPV (categories 1 and 2; SMD = -0.10, 95% CI -0.24 to 0.04), nor was a final BVCA difference found between SB and PPV (SMD = 0.01, 95% CI -0.05 to 0.08), combined SB + PPV and PPV (SMD = 0.02, 95% CI -0.08 to 0.12), or combined SB + PPV and SB (SMD = 0.01, 95% CI -0.11 to 0.12). SB had an elevated risk of choroidal detachment (RR = 5.17, 95% CI 1.68-15.97), hypotony (RR = 12.26, 95% CI 1.63-92.04), and strabismus or diplopia (RR = 5.86, 95% CI 1.04-32.91) compared with PPV but a lower risk of iatrogenic breaks (RR = 0.08, 95% CI 0.02-0.43). Vertical metamorphopsia scores were superior for PnR over PPV at 12 months (Pneumatic Retinopexy versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial, p = 0.026). CONCLUSION: This novel classification system may be useful for future trials assessing morphologic categories of RRD in a systematic manner. Minimally invasive detachment surgery may allow for trials to focus on maximizing functional outcomes while minimizing morbidity.

Changes in aqueous and vitreous inflammatory cytokine levels in proliferative diabetic retinopathy: a systematic review and meta-analysis.

BACKGROUND: Diabetic retinopathy is a major complication of diabetes mellitus, where in its most advanced form ischemic changes lead to the development of retinal neovascularization, termed proliferative diabetic retinopathy (PDR). While the development of PDR is often associated with angiogenic and inflammatory cytokines, studies differ on which cytokines are implicated in disease pathogenesis and on the strength of these associations. We therefore conducted a systematic review and meta-analysis to quantitatively assess the existing body of data on intraocular cytokines as biomarkers in PDR. METHODS: A comprehensive search of the literature without year limitation was conducted to January 18, 2021, which identified 341 studies assessing vitreous or aqueous cytokine levels in PDR, accounting for 10379 eyes with PDR and 6269 eyes from healthy controls. Effect sizes were calculated as standardized mean differences (SMD) of cytokine concentrations between PDR and control patients. RESULTS: Concentrations (SMD, 95% confidence interval, and p-value) of aqueous IL-1ß, IL-6, IL-8, MCP-1, TNF-α, and VEGF, and vitreous IL-2, IL-4, IL-6, IL-8, angiopoietin-2, eotaxin, erythropoietin, GM-CSF, GRO, HMGB-1, IFN-γ, IGF, IP-10, MCP-1, MIP-1, MMP-9, PDGF-AA, PlGF, sCD40L, SDF-1, sICAM-1, sVEGFR, TIMP, TNF-α, and VEGF were significantly higher in patients with PDR when compared to healthy nondiabetic controls. For all other cytokines no differences, failed sensitivity analyses or insufficient data were found. CONCLUSIONS: This extensive list of cytokines speaks to the complexity of PDR pathogenesis, and informs future investigations into disease pathogenesis, prognosis, and management.

Retinal displacement following rhegmatogenous retinal detachment: A systematic review and meta-analysis.

Retinal displacement following rhegmatogenous retinal detachment (RRD) repair is an important consideration when assessing the integrity of reattachment, with potential implications on functional outcomes. There are limited data comparing various surgical techniques. We conducted a review of retinal displacement following RRD repair through October 2021, finding 21 studies encompassing 1,258 unique eyes. Outcome measures included the frequency of retinal displacement, visual acuity, metamorphopsia, and displacement direction. A meta-analysis was performed with data reported as risk ratios (RR) or mean difference and 95% confidence intervals. Retinal displacement was found in 35 ± 20% of RRD repairs. Scleral buckle (SB) without tamponade had the lowest rate of retinal displacement, followed by pneumatic retinopexy (PnR) and finally pars plana vitrectomy (PPV) (RR in PPV vs SB: 9.60 [2.01-45.95], P = 0.005). Silicone oil may reduce risk of displacement following PPV compared to gas (RR in gas vs SO: 2.16 [1.22-3.83], P = 0.009), as may immediate face-down positioning for 2 hours. Retinal displacement following PPV occurred in the downward direction in 92 ± 14% of cases and does not appear to significantly impact visual acuity (0.05 [-0.21 to 0.31], P = 0.70), although it may increase distortion. SB, PnR, PPV with silicone oil, and immediate face-down positioning are likely associated with less retinal displacement. Additional prospective studies are required to increase the certainty of these findings.

Changes in aqueous and vitreous inflammatory cytokine levels in diabetic macular oedema: a systematic review and meta-analysis.

Diabetic macular oedema (DME) is considered a chronic inflammatory disease associated with aberrations in many intraocular cytokines. Studies assessing the role of these cytokines as biomarkers in the diagnosis and management of DME have demonstrated inconsistent findings. We quantitatively summarized data related to 116 candidate aqueous and vitreous inflammatory cytokines as biomarkers in DME. A systematic search without year limitation was performed up to 19 October 2020. Studies were included if they provided data on aqueous or vitreous cytokine concentrations in patients with DME. Effect sizes were generated as standardized mean differences (SMDs) of cytokine concentrations between patients with DME and controls. Data were extracted from 128 studies that included 4163 study eyes with DME and 1281 control eyes. Concentrations (standard mean difference, 95% confidence interval and p-value) of aqueous IL-6 (1.28, 0.57-2.00, p = 0.004), IL-8 (1.06, 0.74-1.39, p < 0.00001), MCP-1 (1.36, 0.57-2.16, p = 0.0008) and VEGF (1.31, 1.01-1.62, p < 0.00001) and vitreous VEGF (2.27, 1.55-2.99, p < 0.00001) were significantly higher in patients with DME (n = 4163) compared to healthy controls (n = 1281). No differences, failed sensitivity analyses or insufficient data were found between patients with DME and healthy controls for the concentrations of the remaining cytokines. This analysis implicates multiple cytokine biomarker candidates other than VEGF in DME and clarifies previously reported inconsistent associations. As the therapeutic options for DME expand to include multiple agents with multiple targets, it will be critical to manage the treatment burden with tailored therapy that optimizes outcomes and minimizes treatment burden. Intraocular cytokines have the promise of providing a robust individualized assessment of disease status and response to therapy. We have identified key candidate cytokines that may serve as biomarkers in individualized treatment algorithms.

Surgical Masks May Hide Neurological Diagnoses.

COVID-19 has disrupted the routine flow of patients through emergency departments (EDs) across the globe, including the need to consider COVID-19 for nearly all presenting complaints. The constraints of mask wearing and isolation have created inherent barriers to timely stroke care. We present a case that highlights one of the many ways in which the pandemic has negatively impacted the care of the non-COVID patient. A patient presented to the ED with a chief complaint of diffuse weakness and a new-onset cough on awakening. His daughter noted that he was slurring his words. An emergency medicine resident evaluated him, ordered laboratory studies, and decided to monitor the patient. The same resident later noted the patient veering to the left when walking, prompting a more detailed neurological examination. On removing the patient's facemask, a left lower facial weakness was evident. The resident called a Code Stroke roughly 50 min after the patient initially presented to the ED. The patient proved to have an acute infarct at the right thalamocapsular junction. Universal masking policies during the COVID-19 pandemic should not prevent the routine assessment of cranial nerve function for all patients presenting to an ED.

A Stepwise Approach to the Surgical Management of Hemorrhagic Choroidal Detachments.

Purpose: This work describes a stepwise surgical approach to draining choroidal detachments and 2 cases for which this approach was used. Methods: The first step involves insertion of an anterior chamber maintainer and a nonvalved 23- or 25-gauge trocar cannula at the highest peak of hemorrhagic choroidal detachment (as determined using B-scan ultrasonography), 6 to 8 mm from and angled 20° to 30° toward the limbus. The second step involves removal of the trocar to expose the sclerotomy. Alternatively, the second step can be insertion of a second trocar. The third step involves the creation of a small focal peritomy around the preexisting sclerotomy and enlargement of the preexisting sclerotomy into a radial sclerotomy. Progression between steps only occurs if prior steps did not provide adequate drainage. Results: Two cases of appositional hemorrhagic choroidal detachments in hypotonic eyes were successfully resolved by this stepwise approach. In case 1, a choroidal detachment developed after a corneal ulcer perforation. The hemorrhagic choroidal detachment in case 1 was resolved with steps 1 and 2, and an unnecessary scleral cutdown was avoided. In case 2, a choroidal detachment developed after a trabeculectomy. The detachment in case 2 required progression to step 3, extension of the trocar insertion site into a radial sclerotomy. Conclusions: This stepwise approach should be considered to reduce excessive manipulation of the globe and conjunctiva in hemorrhagic and serous choroidal detachments that warrant surgical intervention.

Optimizing Color Performance of the Ngenuity 3-Dimensional Visualization System.

Purpose: To evaluate the effect of surgeon-controlled parameters on the color performance of the Ngenuity 3-dimensional (3D) visualization system. Design: A calibrated reference target was placed inside a model eye to assess the Ngenuity 3D camera under different settings. The Ngenuity 3D display was assessed with a commercial colorimeter. Methods: Manufacturer-recommended methodology for white balancing was compared against all common deviations in technique. Following white balance, images of a calibrated reference target were extracted and tested using Imatest Master software to calculate quantitative color differences (delta E and delta C). The Ngenuity monitor was assessed using a SpyderX Elite commercial colorimeter to assess for image burn-in by quantifying color uniformity and maximum luminescence. Main Outcome Measures: Delta E and delta C were calculated for all variables. Color uniformity and luminance were assessed in candelas per square meter (nits). Results: Color performance using the manufacturer-recommended specifications yielded a delta E of 12.81 ± 1.67. Changing the white balance target to a videography grey card (P = 0.07) and 4 × 4 gauze (P = 0.37) provided similar performance, whereas using white computer paper or the operator's palm significantly increased the delta E from 12.81 ± 1.67 to 15.28 ± 1.22 (P = 0.01) and 17.71 ± 2.03 (P < 0.01), respectively. Changes to card position, magnification, stability, or ambient lighting did not significantly impact white balance results, whereas having the card in crisp focus did decrease color accuracy (15.78 ± 1.63; P = 0.03). Minor improvement in performance occurred when the laser filter was off for white balance and image acquisition (9.28 ± 0.25; P < 0.01), but deterioration occurred if the laser filter was placed after balancing (16.59 ± 1.17; P < 0.01). Both light sources of 23-gauge light pipe at 34% intensity and 25-gauge chandelier at 50% intensity gave similar color accuracy (P = 0.37). When comparing different Ngenuity machines, color uniformity and maximum luminescence decreased with increased device use. Conclusions: Overall, the Ngenuity 3D has robust color performance. A few limitations of both the camera and monitor were identified, and surgeons should be aware of these pitfalls as well as solutions examined herein to mitigate their effects during surgery.

Changes in aqueous and vitreous inflammatory cytokine levels in neovascular age-related macular degeneration: a systematic review and meta-analysis.

Inflammatory cytokines are involved in the pathogenesis of neovascular age-related macular degeneration (nAMD) and have been shown to be useful as diagnostic and predictive biomarkers. Given the heterogeneity of data within the literature, we aimed to quantitatively summarize data related to inflammatory cytokines in nAMD. A systematic search without year limitation was performed up to 13 April 2020. Studies were included if they provided data on aqueous or vitreous cytokine concentrations in patients with nAMD. Data were extracted from 95 studies that encompassed 3105 study eyes with nAMD and 1209 control eyes. Effect sizes were generated as standardized mean differences (SMDs) of cytokine concentrations between patients with nAMD and controls. Among the 4314 eyes in 95 studies, aqueous concentrations (standard mean difference, 95% confidence interval and p-value) of MCP-1 (0.43, 0.09 to 0.77 and p = 0.01), MIG (0.63, 0.31 to 0.94 and p = 0.0001), TGF-ß (0.45, 0.07 to 0.82 and p = 0.02) and VEGF (0.64, 0.31 to 0.98 and p = 0.0001) were significantly higher in patients with nAMD compared to healthy controls. No differences, failed sensitivity analyses or insufficient data were found between patients with nAMD and healthy controls for the concentrations of the remaining cytokines and with all vitreous samples. Previous studies had shown conflicting associations with nAMD for all 27 cytokines assessed. Our analysis indicates multiple candidate cytokines other than VEGF that are implicated in nAMD and adds clarity to the previous literature. This will help focus translational research in nAMD investigating biomarkers and therapeutic targets.

Noninfectious endophthalmitis following intravitreal triamcinolone acetonide: clinical case and literature review.

OBJECTIVE: To review the literature on noninfectious endophthalmitis (NIE) following intravitreal triamcinolone acetonide (IVTA). DESIGN: A literature review and case report. PARTICIPANTS: Individuals who developed NIE after IVTA injection. METHODS: A review of the literature was undertaken using Ovid MEDLINE and EMBASE databases, and articles available up to and including December 30, 2019, were included. A total of 518 articles were identified, of which 27 were selected. We also present an illustrative case report. RESULTS: The incidence rate of NIE lies between 0.1% and 7.3% in most studies. Although the etiology of NIE is still the subject of investigation, proposed mechanisms include excipients and rheologic stress caused by small crystals. The time to presentation of NIE is often 1-3 days after IVTA injection, with symptoms of moderate to marked reduction in visual acuity along with signs of anterior chamber inflammatory reaction, hypopyon, and vitritis. Resolution occurs in 1-3 weeks in the majority of patients, and almost all return to their pre-injection visual acuity. Differences in the presentations of NIE, infectious endophthalmitis, and pseudo-endophthalmitis are discussed. We also present an illustrative case report of an 80-year-old woman who developed NIE after an IVTA injection for cystoid macular edema. CONCLUSIONS: It is important to distinguish NIE from other forms of endophthalmitis because they have different natural histories and require different interventions and follow-up. NIE is rarely accompanied by significant pain or conjunctival erythema. Visual acuity is inconsistently affected and is therefore not a good criterion for identifying the type of presenting endophthalmitis.

Changes in Aqueous and Vitreous Inflammatory Cytokine Levels in Retinal Vein Occlusion: A Systematic Review and Meta-analysis.

Purpose: Evidence suggests that inflammatory cytokines not only play a role in the pathogenesis of retinal vein occlusion (RVO) but also may be useful as biomarkers to predict disease severity and response to treatment. We aimed to quantitatively summarize data on inflammatory cytokines associated with RVO. Methods: A systematic search of peer-reviewed English-language articles was performed without year limitation up to August 19, 2019. Studies were included if they provided data on aqueous or vitreous cytokine concentrations in patients with RVO. Data were extracted from 116 studies that encompassed 3242 study eyes with RVO and 1402 control eyes. Effect sizes were generated as standardized mean differences (SMDs) of cytokine concentrations between patients with RVO vs controls. Results: Among the 4644 eyes in 116 studies, aqueous and vitreous concentrations (SMD, 95% CI, and P value) of interleukin (IL)-6 (aqueous: 1.23, 0.65 to 1.81, P < .001 vitreous: 0.70, 0.49 to 0.90, P < .001), IL-8 (aqueous: 1.11, 0.73 to 1.49, P < .001; vitreous: 1.19, 0.73 to 1.65, P < .001), monocyte chemoattractant protein 1(aqueous: 1.22, 0.72 to 1.72, P < .001; vitreous 1.42, 0.92 to 1.91, P < .001), vascular endothelial growth factor (VEGF) (aqueous: 1.52, 1.09 to 1.94, P < .001; vitreous: 0.99, 0.78 to 1.21, P < .001) were significantly higher in patients with RVO than in healthy controls. Only aqueous concentrations of IL-10 (0.81, 0.45 to 1.18, P < .001), angiopoietin 4 (1.96, 0.92 to 3.00, P < .001), and platelet-derived growth factor (PDGF)-AA (0.82, 0.35 to 1.30, P < .001) were significantly higher in patients with RVO than in healthy controls. Only the vitreous concentration of soluble intercellular adhesion molecule-1 (sICAM-1) (1.23, 0.83 to 1.63, P < .001) was significantly higher in patients with RVO. No differences, failed sensitivity analyses, or insufficient data were found between patients with RVO and healthy controls for the concentrations of the remaining cytokines. Conclusions: Several cytokines in addition to VEGF have the potential to be useful biomarkers and therapeutic targets in RVO.

Teaching Flight Nurses Ultrasonographic Evaluation of Esophageal Intubation and Pneumothorax.

Aeromedical prehospital care has seen an increase in the use of point-of-care-ultrasound (POCUS) in recent years. Prior research has focused on abdominal trauma exams by physician or advanced practice providers. In this study, we describe the implementation of an ultrasound curriculum designed for Flight Nurse assessment of pneumothorax and esophageal intubation. The study team conducted three one-hour training sessions over two months. The training curriculum included didactic and hands-on components. We enrolled twelve flight nurses with no prior ultrasound experience. A pre- and post-test was administered consisting of fifteen questions. The median pre-test score was seven correct for an average of 45.0%. After the training session, the median post-test score was fourteen correct for an average of 90.6%. The training intervention resulted in an average improvement in score of 45.6%. While not examining skill acquisition, we are encouraged by the implementation of this curriculum for future ultrasound education in esophageal intubation and pneumothorax.