Infiltration of Proinflammatory M1 Macrophages into the Outer Retina Precedes Damage in a Mouse Model of Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a major cause of blindness in the developed world. Oxidative stress and inflammation are implicated in AMD, but precise mechanisms remain poorly defined. Carboxyethylpyrrole (CEP) is an AMD-associated lipid peroxidation product. We previously demonstrated that mice immunized with CEP-modified albumin developed AMD-like degenerative changes in the outer retina. Here, we examined the kinetics of lesion development in immunized mice and the presence of macrophages within the interphotoreceptor matrix (IPM), between the retinal pigment epithelium and photoreceptor outer segments. We observed a significant and time-dependent increase in the number of macrophages in immunized mice relative to young age-matched controls prior to overt pathology. These changes were more pronounced in BALB/c mice than in C57BL/6 mice. Importantly, IPM-infiltrating macrophages were polarized toward the M1 phenotype but only in immunized mice. Moreover, when Ccr2-deficient mice were immunized, macrophages were not present in the IPM and no retinal lesions were observed, suggesting a deleterious role for these cells in our model. This work provides mechanistic evidence linking immune responses against oxidative damage with the presence of proinflammatory macrophages at sites of future AMD and experimentally demonstrates that manipulating immunity may be a target for modulating the development of AMD

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Opacification of Akreos Hydrophilic Acrylic Lens After Retinal Detachment Repair with Silicone Oil Tamponade: A Case Report

We report localized opacification of a sclera-fixated Akreos hydrophilic acrylic intraocular lens after successful repair of rhegmatogenous retinal detachment with silicone oil tamponade in a nondiabetic patient. No intraoperative lens opacification during air-fluid exchange or lens dislocation was encountered. Granular opacities within the optic were noted at 5 months after surgery, and did not relent to scrubbing with a vitrector during oil removal. Akreos lens opacification under silicone oil is not well documented in the literature. Surgeons must be aware of this potential complication, which is known to occur with various types of hydrophilic acrylic lenses after exposure to air or gas

Choroidal calcifications in two cases of aplasia cutis congenita and oculoectodermal syndrome

To describe choroidal calcifications as an ophthalmic feature in aplasia cutis congenita (ACC) with oculoectodermal syndrome (OES). Two cases of ACC/OES with characteristic echographic evidence of choroidal calcifications are described. The ophthalmic manifestations of ACC/OES may be expanded to include choroidal calcifications. The presence of a choroidal calcification with B-scan ultrasound in a case suspicious for ACC/OES may facilitate a more timely diagnosis and inform future follow-up regimens to monitor ophthalmic and systemic manifestations of this disease

Superficial and Deep Capillary Plexus Nonperfusion in Nonaccidental Injury on OCTA

Purpose: To report OCTA findings in a case of nonaccidental injury (NAI). Methods: Retrospective review of a clinical case. Results: A 5-year-old White child with a history of NAI at age 1 year presented with reduced vision in the left eye resulting from a closed funnel retinal detachment. The right eye had optic nerve pallor, peripheral vascular attenuation, and leakage. Optical coherence tomography angiography (OCTA) showed significant parafoveal attenuation of the superficial vascular plexus, intermediate capillary plexus, and deep capillary plexus. This correlated with inner and middle retinal layer thinning temporal to the fovea and preservation of the ellipsoid zone. The peripapillary vascular plexus was preserved. Laser photocoagulation was performed to the nonperfused peripheral retina, and intravitreal bevacizumab was injected. Attenuation of the superficial, intermediate, and deep capillary plexuses might represent chronic ischemic retinal changes from traumatic injury to the vitreoretinal interface and inner retina in NAI. Conclusions: OCTA identified nonperfusion of the superficial and deep vascular plexuses as late sequelae of NAI. Traumatic injuries to the vitreoretinal interface in NAI might lead to inner retinal ischemia and atrophy with vascular attenuation present on OCTA

Intravitreal rituximab for the treatment of a secondary intraocular relapse of a large B-cell lymphoma

Purpose: To report a rare case of secondary intraocular lymphoma treated with intravitreal rituximab, following pars plana vitrectomy. Observations: A 74-year-old female with history of parotid gland large B-cell lymphoma presented bilateral intraocular recurrence 10 years after the onset of the primary malignancy. Systemic work-up including PET/CT Scan, bone marrow biopsy, brain MRI and CSF analysis were unremarkable, and the patient declined to undergo systemic chemotherapy. Vision loss in her left eye was severe due to significant sub-retinal pigment epithelium (RPE) infiltration involving the macula; this eye was treated with external beam radiation therapy. On the right eye, the relapse manifested with vitreous involvement and fovea-sparing multifocal, sub-RPE infiltration for which the patient received monthly intravitreal rituximab injections, following pars plana vitrectomy. Through the course of therapy, the patient achieved good local control and maintained 20/20 visual acuity on her right eye. Brain magnetic resonance imaging (MRI) surveillance, every 3 months, was performed and revealed a cerebellar recurrence 24 months into the course of therapy. Conclusions and importance: Our case illustrates how intravitreal immunotherapy with rituximab may provide local control of CD-20 positive secondary intraocular lymphoma; particularly in cases where systemic therapy is not amenable. In our case, a prior vitrectomy, did not appear to interfere with the therapeutic effect of intravitreal rituximab. Close quarterly surveillance with Brain MRI may help disclose central nervous system recurrences in such cases

Intravitreal rituximab for the treatment of a secondary intraocular relapse of a large B-cell lymphoma

Purpose: To report a rare case of secondary intraocular lymphoma treated with intravitreal rituximab, following pars plana vitrectomy. Observations: A 74-year-old female with history of parotid gland large B-cell lymphoma presented bilateral intraocular recurrence 10 years after the onset of the primary malignancy. Systemic work-up including PET/CT Scan, bone marrow biopsy, brain MRI and CSF analysis were unremarkable, and the patient declined to undergo systemic chemotherapy. Vision loss in her left eye was severe due to significant sub-retinal pigment epithelium (RPE) infiltration involving the macula; this eye was treated with external beam radiation therapy. On the right eye, the relapse manifested with vitreous involvement and fovea-sparing multifocal, sub-RPE infiltration for which the patient received monthly intravitreal rituximab injections, following pars plana vitrectomy. Through the course of therapy, the patient achieved good local control and maintained 20/20 visual acuity on her right eye. Brain magnetic resonance imaging (MRI) surveillance, every 3 months, was performed and revealed a cerebellar recurrence 24 months into the course of therapy. Conclusions and importance: Our case illustrates how intravitreal immunotherapy with rituximab may provide local control of CD-20 positive secondary intraocular lymphoma; particularly in cases where systemic therapy is not amenable. In our case, a prior vitrectomy, did not appear to interfere with the therapeutic effect of intravitreal rituximab. Close quarterly surveillance with Brain MRI may help disclose central nervous system recurrences in such cases