Spindle Cell Carcinoma of the Ocular Adnexa: A Case Report and Literature Review.

A 68-year-old woman was seen in oculoplastic consultation with a medial canthal lesion initially diagnosed as an atypical fibroxanthoma. On excisional biopsy, she was found to have a spindle cell carcinoma, which is a rare and reportedly more aggressive form of squamous cell carcinoma. We highlight the surgical technique of biopsy and reconstruction, the detailed histologic and immunohistochemical analysis required for accurate diagnosis, considerations for adjuvant treatment, and suggestions for systemic workup and surveillance. This case adds to the small body of available literature on primary spindle cell carcinoma of the ocular surface and ocular adnexa, which we have summarized. We hope that as more data becomes available, there will be clearer diagnostic and treatment algorithms for this uncommon presentation.

Inadvertent Orbital Mitomycin C Injection as a Cause of Ptosis and Ophthalmoplegia from Orbital Necrosis.

Mitomycin C is an alkylating agent with the ability to suppress fibroblast proliferation and activity, making it a powerful antifibrotic. It has therefore become popular in glaucoma filtering surgeries, used both intraoperatively during bleb formation and postoperatively as an adjunct to bleb needling. This report presents a rare but serious risk of bleb needling with Mitomycin C at the slit lamp, where inadvertent movement of the patient resulted in an orbital injection. The patient quickly developed focal tissue inflammation and necrosis, presenting one day after the procedure with complete ptosis, ophthalmoplegia, and a palpable orbital mass. After appropriate imaging and an excisional biopsy to exclude infectious, infiltrative, and neoplastic causes, this was managed with close observation and continued improvement, and resolution of most orbital sequelae.

A marine biogenic source of atmospheric ice-nucleating particles.

The amount of ice present in clouds can affect cloud lifetime, precipitation and radiative properties. The formation of ice in clouds is facilitated by the presence of airborne ice-nucleating particles. Sea spray is one of the major global sources of atmospheric particles, but it is unclear to what extent these particles are capable of nucleating ice. Sea-spray aerosol contains large amounts of organic material that is ejected into the atmosphere during bubble bursting at the organically enriched sea-air interface or sea surface microlayer. Here we show that organic material in the sea surface microlayer nucleates ice under conditions relevant for mixed-phase cloud and high-altitude ice cloud formation. The ice-nucleating material is probably biogenic and less than approximately 0.2 micrometres in size. We find that exudates separated from cells of the marine diatom Thalassiosira pseudonana nucleate ice, and propose that organic material associated with phytoplankton cell exudates is a likely candidate for the observed ice-nucleating ability of the microlayer samples. Global model simulations of marine organic aerosol, in combination with our measurements, suggest that marine organic material may be an important source of ice-nucleating particles in remote marine environments such as the Southern Ocean, North Pacific Ocean and North Atlantic Ocean.

Sea spray aerosol as a unique source of ice nucleating particles.

Ice nucleating particles (INPs) are vital for ice initiation in, and precipitation from, mixed-phase clouds. A source of INPs from oceans within sea spray aerosol (SSA) emissions has been suggested in previous studies but remained unconfirmed. Here, we show that INPs are emitted using real wave breaking in a laboratory flume to produce SSA. The number concentrations of INPs from laboratory-generated SSA, when normalized to typical total aerosol number concentrations in the marine boundary layer, agree well with measurements from diverse regions over the oceans. Data in the present study are also in accord with previously published INP measurements made over remote ocean regions. INP number concentrations active within liquid water droplets increase exponentially in number with a decrease in temperature below 0 °C, averaging an order of magnitude increase per 5 °C interval. The plausibility of a strong increase in SSA INP emissions in association with phytoplankton blooms is also shown in laboratory simulations. Nevertheless, INP number concentrations, or active site densities approximated using "dry" geometric SSA surface areas, are a few orders of magnitude lower than corresponding concentrations or site densities in the surface boundary layer over continental regions. These findings have important implications for cloud radiative forcing and precipitation within low-level and midlevel marine clouds unaffected by continental INP sources, such as may occur over the Southern Ocean.

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

OBJECTIVE: Diabetic retinopathy is a complication of diabetes mellitus with the potential for significant patient morbidity. Although changes to intraocular inflammatory cytokines are integral to disease pathogenesis, studies have been inconsistent about which exact cytokines are associated with diabetic retinopathy. We aimed to quantitatively summarize proangiogenic and proinflammatory cytokines in nonproliferative diabetic retinopathy (NPDR), given its frequency among those with diabetes mellitus. METHODS: A systematic literature search without year limitation to February 21, 2022, identified 59 studies assessing vitreous or aqueous cytokine levels in NPDR, encompassing 1378 eyes with NPDR and 1288 eyes from nondiabetic controls. Effect sizes were generated as standardized mean differences (SMD) of cytokine concentrations between patients with NPDR and controls. RESULTS: Concentrations (SMD, 95% confidence interval, and p value) of aqueous interleukin-6 (IL-6) (2.58, 1.17‒3.99; p = 0.0003), IL-8 (1.56, 0.39‒2.74; p = 0.009), IL-17 (13.55, 7.50‒19.59; p < 0.001), transforming growth factor beta (TGF-ß) (2.44, 1.02‒3.85; p = 0.0007) and vascular endothelial growth factor (VEGF) (1.35, 0.76‒1.93; p < 0.00001), and vitreous VEGF (1.49, 0.60‒2.37; p = 0.001) were significantly higher in patients with NPDR when compared with those of healthy controls. CONCLUSIONS: These cytokines may serve as disease markers of the biochemical alterations seen in NPDR and may guide interventions, as we move into an era of more targeted therapeutics.

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.

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 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.

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.