Risk of Proliferative Vitreoretinopathy in the Second Eye in Adult Patients with Bilateral Retinal Detachment.

PURPOSE: To examine the incidence and risk factors of proliferative vitreoretinopathy (PVR) in the patients who develop rhegmatogenous retinal detachment (RRD) in their fellow eye after having a prior RRD complicated by PVR. DESIGN: Multicenter, retrospective observational study. SUBJECTS: Eyes with retinal detachment and PVR between 2015 and 2023 were identified through the Vestrum Health Database METHODS: Risk factors for PVR development, specifically documented PVR in the fellow eye, gender, age, lens status, and presenting and final visual acuity, were evaluated. MAIN OUTCOME MEASURES: Odds ratio for PVR development during 6 months post-operative period. RESULTS: Of 57,264 patients, 11% had PVR in at least one eye. Of the 50,989 patients who did not develop PVR after the initial RRD, 4,834 developed RRD in the fellow eye. 166 of these patients developed PVR in their second eye for a PVR rate of 3% in the fellow eye. Of the 6,275 patients who developed PVR after primary RRD repair, 406 of these patients went on to develop RRD in their fellow eye. 42 of these patients developed PVR in their second eye for a PVR rate of 10%. A regression model that also included age, gender and visual acuity led to an odds ratio of 3.42 (p<0.001). The odds ratio of PVR development generally decreased with age. Pseudophakic patients had a higher odds ratio for PVR development, 1.48 (p=0.017). Initial patients with VA 20/40-20/80 had an odds ratio of 2.15 (p=0.003). Patients with VA worse than 20/200 had an odds ratio of 2.89 for PVR development (p<0.001). CONCLUSIONS: Patients with a history RRD with PVR in one eye, have approximately 3.5 times higher rate of PVR in their second eye after RRD compared with patients without a history of PVR. This finding potential impacts surgical decisions and use of prophylactic anti-PVR therapy if the patient's second eye has RRD. The final visual acuity in second eye of patients with history PVR is better than for the second eye of patients with no history of PVR which may indicate surgeons are already taking steps to prevent PVR in the patient's second eye.

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.

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.

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.

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.

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.

Antibody-free reading of the histone code using a simple chemical sensor array.

The histone code refers to the complex network of histone post-translational modifications that control gene expression and are of high interest as drivers of a large number of human diseases. We report here on a mix-and-match toolkit of readily available dyes and calixarene host molecules that can be combined to form dye-displacement sensors that respond to a wide variety of cationic peptides. Using the data from only two or three such simple supramolecular sensors as a chemical sensor array produces fingerprints of data that discriminate robustly among many kinds of histone code elements. "Reads" that are accomplished include the discrimination of unmethylated, mono-, di-, and trimethylated lysines on a single histone tail sequence, identification of different modifications and combinations of modifications on a single histone tail sequence, identification of a single modification type in several different sequence contexts, and identification of isomeric dimethylarginine modifications. Reads that are sometimes troublesome for antibodies are achieved. We also report on the ability of the sensor array to report simultaneously on the concentrations and identities of histone modifications. This sensor array discriminates between post-translationally modified analytes without being limited to partners that contain a single, programmed binding interaction.

Tetra-µ-acetato-κO:O'-bis-[(3-cyano-pyridine-κN)ruthenium(II,III)](Ru-Ru) hexa-fluoridophosphate 1,2-dichloro-ethane monosolvate.

The title compound, [Ru(2)(CH(3)CO(2))(4)(C(6)H(4)N(2))(2)]PF(6)·C(2)H(4)Cl(2), was obtained via a rapid substitution reaction in 2-propanol whereby 3-cyano-pyridine replaces the axial water mol-ecules in the diaquatetra-µ-acetato-diruthenium(II,III) hexa-fluorido-phosphate starting material. The product rapidly precipated and crystals were grown from 1,2-dichloro-ethane. The 1,2-dichloro-ethane mol-ecule of solvation exhibits disorder with two different orientations [occupancy ratio 0.51 (6):0.49 (6)]. All three parts, the cation, the anion and the disordered solvent mol-ecule lie on crystallographic inversion centers. The Ru-Ru bond length of 2.2702 (6) Šfits nicely into the range seen for similar complexes and correlates well with the reduction potential of the complex and donor strength of the axial ligand, 3-cyano-pyridine, as postulated in a previous study [Vamvounis et al. (2000 ▶). Inorg. Chim. Acta, 305, 87-98]. The 3-cyano-pyridine ligands orient themselves in an anti configuration with respect to each other and the Ru-Ru-N angle [174.27 (7)°] is close to being linear.