Mapping 123 million neonatal, infant and child deaths between 2000 and 2017.

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2-to end preventable child deaths by 2030-we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000-2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations.

Does the ISNT rule apply to the radial peripapillary capillary vessel density in OCT angiography?

PURPOSE: To investigate the applicability of ISNT (inferior ≥ superior ≥ nasal ≥ temporal), IST (inferior ≥ superior ≥ temporal), and T min (temporal quadrant with the minimum value) rules to the peripapillary nerve fiber layer (NFL) thickness and radial peripapillary capillary (RPC) vessel density (VD) using Optical Coherence Tomography (OCT) and OCT angiography (OCT-A). MATERIALS AND METHODS: This cross-sectional study included 134 eyes of 74 healthy individuals. NFL thickness and RPC VD were measured in all four quadrants using OCT and OCT-A in order to determine the number of eyes that obey the ISNT, IST, and T min rules. RESULTS: Mean age was 48.8 ± 15.5 (range 25-82) years. The ISNT rule was valid in 52 eyes (38.81%) on OCT and only 12 eyes (8.95%) on OCT-A scans. The IST rule was followed by 83 (61.94%) and 37 (27.61%) eyes on OCT and OCT-A scans respectively. The T min rule was valid in 86 eyes (64.18%) in OCT scans and in 26 eyes (19.4%) in OCT-A scans. CONCLUSION: The topography of the RPC network does not obey the ISNT rule in healthy eyes. The ISNT rule and its variants were found to be more relevant in OCT NFL thickness measurements compared to OCT-A RPC VD measurements.

Scleral buckling surgery for stage 4A and 4B retinopathy of prematurity in critically ill neonates.

PURPOSE: To determine the efficacy of scleral buckling in eyes with stage 4A and 4B retinopathy of prematurity (ROP). METHODS: Seven eyes of five premature infants underwent scleral buckling for stage 4 ROP in zone II. Five eyes had stage 4A ROP, and two eyes had stage 4B ROP. Six eyes had previous diode laser photocoagulation, and one eye had received an intravitreal ranibizumab injection. Scleral buckling was the procedure of choice due to lack of access to specialized pediatric vitrectomy instrumentation. Average age at surgery was 3.4 months. Postoperative anatomic retinal status, visual acuity outcome and refractive error were assessed. RESULTS: The scleral buckle was removed on average 8 months after surgery. Retinal reattachment was achieved in all seven eyes. At final follow-up one eye had macular ectopia and disc dragging, one eye had a macular traction fold and two eyes had optic disc pallor. Average myopic error after buckle removal was -7.5 D. CONCLUSION: Scleral buckling can be performed safely and effectively in 4A and 4B stage ROP in critically ill infants, when access to specialized pediatric vitrectomy instrumentation is limited. This surgical technique may provide adequate relief of vitreoretinal traction with improved visual potential.

Macular sequelae in vasoproliferative tumors: results of surgical approach.

PURPOSE: The purpose of this study is to report the clinical manifestations and treatment outcomes in three patients diagnosed with vasoproliferative tumors (VPTs). METHODS: A retrospective, single-center case series was conducted, and retinal findings from three cases were documented by clinical examination and multimodal imaging. RESULTS: Three patients presented with an elevated, yellow-white retinal lesion located at the peripheral retina and extensive retinal exudation. All three patients were closely monitored, and tumor-associated features included lipid exudates, cystoid macular edema (CMO), pre-retinal fibrosis and epi-retinal membrane (ERM). Clinical management relied on observation, cryotherapy, laser photocoagulation, intravitreal steroids and anti-vascular endothelial growth factor (anti-VEGF) treatment. Despite different clinical courses, two patients underwent vitreo-retinal surgery to address VPT-related complications of macular hole and vitreo-macular traction, whereas a patient underwent phacoemulsification to treat steroid-induced cataract. CONCLUSION: VPTs are uncommon benign vascular tumors and usually located at the infero-temporal peripheral retina. Close observation and early diagnosis of VPTs are of great importance in preventing vision-threatening complications and ensuring the best final visual outcome. The optimal treatment has yet to be defined due to lack of multi-center clinical studies. Despite the availability of less invasive therapeutic interventions, however, our case series show that pars plana vitrectomy is sometimes the most appropriate choice to restore visual acuity.

Anti-platelet effects of vitamin supplements in age-related macular degeneration: an in vitro study.

OBJECTIVE: The purpose of this experimental study was to investigate the role of vitamin supplements (Ocuvite, Vitalux Omega, and Nutrof Total) as possible inhibitors of the onset of age-related macular degeneration (AMD). MATERIALS AND METHODS: The anti-aggregating effect of each vitamin was determined against four accumulative factors namely, platelet activating factor (PAF), adenosine diphosphate (ADP), thrombin receptor-activating peptide (TRAP), and arachidonic acid (AA) in the platelet rich plasma (PRP) of healthy volunteers. RESULTS: Ocuvite, Vitalux Omega, and Nutrof Total were more potent inhibitors against PAF and ADP compared to TRAP and AA. Among the three vitamins, Nutrof Total displayed more potent inhibitions against TRAP and AA, while against PAF and ADP all the three vitamins revealed similar IC50 values. CONCLUSIONS: The vitamins Ocuvite, Vitalux Omega, and Nutrof Total have anti-aggregating effects and therefore can be used against AMD in healthy volunteers.

SUTURELESS CLEAR CORNEAL ULTRASONIC FRAGMENTATION FOR RETAINED LENS FRAGMENTS: A Pilot Study.

PURPOSE: To describe the safety and efficacy of removing posteriorly dislocated lens fragments with the use of intravitreal ultrasonic fragmentation through a limbal, clear cornea self-sealing incision. METHODS: Patients presenting with posteriorly luxated nuclei were enrolled in this prospective case series. Preoperative examination included evaluation of the corneal endothelium by means of specular microscopy. A 3-port 25+ pars plana vitrectomy was initially performed. Following vitrectomy, sclerotomies were sealed using scleral plugs and a limbal/clear corneal incision was performed for the insertion of the fragmatome probe. The incision was slightly larger (1 mm) than the diameter of the fragmatome probe (20 gauge = 0.81 mm) to avoid wound overheating. At the end of the procedure, an appropriate intraocular lens either sulcus-fixated or angle-supported was implanted. Primary outcome measures were mean postoperative best-corrected visual acuity, intraoperative or postoperative complications, and intraoperative challenging features. RESULTS: In all eyes, fragmentation was completed successfully with a mean total ultrasound time of 113.4 seconds. Nucleus density was ≥3 in all cases (mean ± SD = 3.8 ± 0.4). Intraoperative challenges included viewing difficulties because of corneal distortion, fragment turbulence, and leakage through the limbal incision potentially compromising fundus visualization. There was statistically nonsignificant reduction in endothelial cell density ranging between 1932 ± 187 cells per square millimeter preoperatively to 1789 ± 213 cells per square millimeter at the first month postoperatively (P = 0.79). CONCLUSION: Clear corneal, sutureless ultrasonic fragmentation seems to be a novel, safe, and efficient method for the removal of hard posteriorly dislocated lens fragments, sparing the need for a 20-gauge scleral port.

Repeatability of Retinal Macular Thickness Measurements in Patients with Clinically Significant Macular Edema Using Two Different Scanning Protocols of Spectralis Optical Coherence Tomography.

OBJECTIVE: To determine the repeatability of Spectralis optical coherence tomography (OCT) retinal thickness measurements in diabetic patients with clinically significant macular edema (CSME) using two different scanning protocols. METHODS: Seventy-one eyes of 71 diabetic patients with CSME were included in the study. Coefficients of repeatability and intrasession variation coefficients were tested with 20 × 15 degree raster scans consisting of 19 or 37 high-resolution line scans (15 or 8 frames per scan, respectively) that were repeated 2 times by 1 experienced examiner. The first scan was set as the reference scan; the second scan was the follow-up scan and was performed with the use of the follow-up mode. RESULTS: The mean and standard deviation for the central foveal subfield (CSF) using the first scanning method was 404 ± 88 µm, while it was 399 ± 86 µm using the second protocol, which was not statistically significantly different (p = 0.35, paired test). Particularly examining the CSF, the coefficient of repeatability was 1.48 (6.00 µm) and 1.49 (5.95 µm) for the 19- and the 37-B-scan acquisition, respectively, showing a nonstatistically significant difference (p < 0.001). CONCLUSIONS: Retinal thickness measurements in diabetic patients with CSME are repeatable using both scanning protocols (19 or 37 B-scans) with Spectralis OCT. The repeatability of the retinal thickness measurement does not improve by increasing the number of B-scans from 19 to 37.

Repeatability of Retinal Macular Thickness Measurements in Healthy Subjects and Diabetic Patients with Clinically Significant Macular Edema: Evaluation of the Follow-Up System of Spectralis Optical Coherence Tomography.

BACKGROUND: It was the aim of this study to compare the repeatability of Spectralis optical coherence tomography (OCT) retinal thickness measurements in healthy subjects and diabetic patients with clinically significant macular edema (CSME) with or without the use of the follow-up system. METHODS: Thirty-eight eyes of 38 healthy subjects (control group) and 68 eyes of 68 diabetic patients with CSME were included in the study. The coefficient of repeatability (CR) and intrasession coefficients of variation were tested with 20 × 15 degree raster scans consisting of 19 high-resolution line scans (15 frames per scan) that were repeated 3 times by 1 experienced examiner. The first scan was set as the reference scan, whereas the second and third scans were the follow-up scans and were performed with and without the use of the follow-up mode, respectively. RESULTS: The means and standard deviations for the central foveal subfield (CSF) in healthy subjects and diabetic patients were 289 ± 21 and 402 ± 105 µm, respectively. Particularly in diabetic patients, examining the CSF, CR was 2.67% (10.73 µm) and 6.73% (27.01 µm) with and without using the follow-up mode, respectively, and the difference was statistically significant (p < 0.05). CONCLUSION: These results support the hypothesis that the follow-up system improves the repeatability either in healthy subjects or in diabetic patients with poor fixation. The wider improvement in repeatability in diabetic patients in the follow-up system group compared to the no follow-up system group are probably related to poor patient fixation or eye movement in patients with CSME.

Optical coherence tomography-guided classification of epiretinal membranes.

To study and classify epiretinal membranes (ERMs) based on spectral domain optical coherence tomography (SD-OCT) findings. One hundred and twelve patients with ERMs were examined clinically and underwent OCT examination. The anatomical structure of the macula and vitreoretinal interface was studied. ERMs were classified in two categories: A, with posterior vitreous detachment (PVD) (91 cases), and B, with the absence of PVD (21 cases). Category A was divided into two subcategories: A1, without contraction of the ERM (37 cases), and A2, with the presence of membrane contraction (54 cases). A2 was further subdivided into A2.1, with retinal folding (15 cases), A2.2, with edema (23 cases), A2.3, with cystoid macular edema (9 cases), and A2.4, with lamellar macular hole (7 cases). Category B was divided in two subcategories: B1, without vitreomacular traction (VMT) (4 cases), and B2, with the presence of VMT (17 cases). Category B2 was subdivided into B2.1, with edema (9 cases), B2.2, presenting retinal detachment (5 cases), and B2.3, with schisis (3 cases). OCT classification of ERMs provides useful information on the anatomical structure of the retina, and the accurate estimation of vitreoretinal interface.

Comparison of interleukin-6 and matrix metalloproteinase expression in the subretinal fluid and the vitreous during proliferative vitreoretinopathy: correlations with extent, duration of RRD and PVR grade.

INTRODUCTION: The full extent of IL-6 involvement in PVR pathophysiology has not yet been comprehensively investigated. The aim of this study was the comparison of the IL-6 effect on MMP expression between SRF and the vitreous in the context of RRD complicated by PVR. MATERIALS AND METHODS: Thirty-one SRF samples from 31 eyes of 31 consecutive patients suffering from RRD with PVR were collected during treatment by scleral buckling. Twenty-eight vitreous samples from 28 eyes of 28 RRD patients with PVR were collected during surgical management with pars plana vitrectomy (PPV). Enzyme Linked Immunosorbent Assay was employed for the measurement of MMP-1, -3, -8 and TIMP-1 concentrations (in ng/ml). MMP gelatinolytic activity was determined with the use of gelatin zymography analysis using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: Correlation analysis in the SRF revealed a significant correlation between MMP-1/IL6 and RRD duration. Regression analysis in the SRF revealed a significant correlation between the MMP-9/IL-6 and RRD extent. In the same fluid, with respect to PVR grade, ANOVA revealed a significant relationship with the proMMP-2/IL-6, MMP-2/IL6 and TIMP-1/IL-6 ratios. Graphical representation of the results revealed that, between the SRF and vitreous groups, significant peak values were observed for all MMP/IL-6 and TIMP-1/IL-6 ratios included in this study with the exception of the MMP-2/IL-6 ratio. CONCLUSIONS: It appears that there is a significant correlation between the presence of IL-6 and MMP/TIMP ratio in the SRF, indicating that IL-6 may contribute to the increased MMP/TIMP ratio during PVR.

Laser flare photometry in eyes receiving brolucizumab intravitreal injections for age related macular degeneration.

PURPOSE: To measure aqueous flare levels in treatment naïve eyes suffering from wet age- related macular degeneration (wAMD) treated with intravitreal brolucizumab. METHODS: Patients with treatment naïve wAMD in one eye were prospectively enrolled. Flare levels were measured with laser flare photometry at baseline, 1 day and 1 month after each of the 3 monthly injections during the loading phase. RESULTS: Twenty-two eyes from 22 patients aged 76.7 ± 6.0 years were enrolled. Flare values were 10.6 ± 3.7 photons/msec at baseline and 12.6 ± 5.8 photons/msec at the last follow up visit, 1 month after the third injection (p = 0.289, repeated measures ANOVA). The mean change in flare after the first injection was 4.2 ± 3.6. photons/msec, 6.6 ± 8.9 photons/msec after the 2nd and 8.6 ± 20.8 photons/msec after the 3rd injection (p = 0.640, repeated measures ANOVA). No patient had clinical signs of intraocular inflammation. CONCLUSIONS: Eyes receiving brolucizumab injections for wAMD showed similar flare at baseline, during and 1 month after completion of three-monthly intravitreal injections. There was no evidence of subclinical inflammation during the loading phase of brolucizumab based on laser flare photometry measurements.

Macular Ischemia Changes in Patients with Diabetic Macular Edema Treated with Aflibercept and Ranibizumab.

Τhis study aims to assess changes in the fovea avascular zone (FAZ) in treatment naïve patients receiving aflibercept or ranibizumab injections for diabetic macular edema (DME). Best corrected visual acuity (BCVA) testing, OCT, and OCT-angiography imaging were performed at baseline and 1 month after each injection. Injections of either aflibercept or ranibizumab were administered monthly for 6 consecutive months. FAZ in the superficial (SCP) and the deep capillary plexus (DCP) using OCT angiography was recorded for each visit. Fifty eyes from fifty patients with a mean age of 67.0 ± 10.7 years were included in the study. Twenty-five patients received aflibercept and twenty-five received ranibizumab. BCVA was 40.8 ± 10.0 and increased to 52.1 ± 7.9 ETDRS letters at the last visit (p < 0.001). CRT was 295.6 ± 34.0 at baseline and 247.9 ± 29.7 at the last study visit (p < 0.001). SCP FAZ was 350.6 ± 79.5 µm2 at baseline and 339.0 ± 71.3 µm2 after sox monthly injections (p = 0.132). DCP FAZ was 558.6 ± 199.0 µm2 at baseline and 459.5 ± 156.1 µm2 after six monthly injections (p < 0.001). There was no effect of the choice of ranibizumab or aflibercept on DCP FAZ change (p = 0.277). In conclusion, treatment with 6 monthly injections of ranibizumab and aflibercept led to an increase in BCVA and a decrease in CRT and DCP FAZ area. Both drugs led to an improvement in DCP ischemia.

Non-Healing Corneal Ulcer and Uveitis Following Monkeypox Disease: Diagnostic and Therapeutic Challenges.

PURPOSE: The ocular manifestations of Monkeypox virus (Mpox) infection remain incompletely characterized. Our goal is to present a case series of non-healing corneal ulcers with associated uveitis caused by Mpox infection as well as management recommendations for Mpox-related ophthalmic disease (MPXROD). METHODS: Retrospective case series. RESULTS: Two male patients with recent hospitalization for systemic Mpox infection presented with non-healing corneal ulcer associated with anterior uveitis and severe IOP elevation. Despite initiation of conservative medical treatment including corticosteroid treatment for uveitis, in both cases, there was clinical progression with enlarging cornea lesions. Both cases received oral tecovirimat with complete healing of the corneal lesion. CONCLUSIONS: Corneal ulcer and anterior uveitis are rare complications of Mpox infection. Although Mpox disease is generally anticipated to be self-limited, tecovirimat may be an effective intervention in poorly healing Mpox keratitis. Corticosteroids should be used with caution in Mpox uveitis, as they might lead to worsening infection.

The Humira in Ocular Inflammations Taper (HOT) Study.

PURPOSE: To assess factors that impact the risk of relapse in patients with noninfectious uveitis (NIU) who undergo adalimumab tapering after achieving remission. DESIGN: Retrospective study. METHODS: In this multicenter study, patients with NIU were treated with adalimumab and subsequently tapered. Patient demographics, type of NIU, onset and duration of disease, the period of inactivity before tapering adalimumab, and the tapering schedule were collected. The primary outcome measures were independent predictors of the rate of uveitis recurrence after adalimumab tapering. RESULTS: Three hundred twenty-eight patients were included (54.6% female) with a mean age of 34.3 years. The mean time between disease onset and initiation of adalimumab therapy was 35.2 ± 70.1 weeks. Adalimumab tapering was commenced after a mean of 100.8 ± 69.7 weeks of inactivity. Recurrence was observed in 39.6% of patients at a mean of 44.7 ± 61.7 weeks. Patients who experienced recurrence were significantly younger than those without recurrence (mean 29.4 years vs 37.5 years, P = .0005), and the rate of recurrence was significantly higher in younger subjects (hazard ratio [HR] = 0.88 per decade of increasing age, P = .01). The lowest rate of recurrence was among Asian subjects. A faster adalimumab taper was associated with an increased recurrence rate (HR = 1.23 per unit increase in speed, P < .0005). Conversely, a more extended period of remission before tapering was associated with a lower rate of recurrence (HR = 0.97 per 10-weeks longer period of inactivity, P = .04). CONCLUSIONS: When tapering adalimumab, factors that should be considered include patient age, race, and duration of disease remission on adalimumab. A slow tapering schedule is advisable.

Secukinumab in the treatment of noninfectious uveitis: results of three randomized, controlled clinical trials.

PURPOSE: To determine the efficacy and safety of different doses of secukinumab, a fully human monoclonal antibody for targeted interleukin-17A blockade, in patients with noninfectious uveitis. DESIGN: Three multicenter, randomized, double-masked, placebo-controlled, dose-ranging phase III studies: SHIELD, INSURE, and ENDURE. PARTICIPANTS: A total of 118 patients with Behçet's uveitis (SHIELD study); 31 patients with active, noninfectious, non-Behçet's uveitis (INSURE study); and 125 patients with quiescent, noninfectious, non-Behçet's uveitis (ENDURE study) were enrolled. METHODS: After an initial subcutaneous (s.c.) loading phase in each treatment arm, patients received s.c. maintenance therapy with secukinumab 300 mg every 2 weeks (q2w), secukinumab 300 mg monthly (q4w), or placebo in the SHIELD study; secukinumab 300 mg q2w, secukinumab 300 mg q4w, secukinumab 150 mg q4w, or placebo in the INSURE study; or secukinumab 300 mg q2w, secukinumab 300 mg q4w, secukinumab 150 mg q4w, or placebo in the ENDURE study. MAIN OUTCOME MEASURES: Reduction of uveitis recurrence or vitreous haze score during withdrawal of concomitant immunosuppressive medication (ISM). Other end points included best-corrected visual acuity, ISM use (expressed as a standardized ISM score), and safety outcomes. RESULTS: After completion or early termination of each trial, there were no statistically significant differences in uveitis recurrence between the secukinumab treatment groups and placebo groups in any study. Secukinumab was associated with a significant reduction in mean total post-baseline ISM score (P = 0.019; 300 mg q4w vs. placebo) in the SHIELD study. Likewise, secukinumab was associated with a greater median reduction in ISM score versus placebo in the INSURE study, although no statistical analysis of the difference was conducted because of the small sample size. Overall, there was no loss in visual acuity reported in any treatment group during follow-up in all 3 studies. According to descriptive safety statistics, the frequencies of ocular and nonocular adverse events seemed to be slightly higher among secukinumab groups versus placebo across the 3 studies. CONCLUSIONS: The primary efficacy end points of the 3 studies were not met. The secondary efficacy data from these studies suggest a beneficial effect of secukinumab in reducing the use of concomitant ISM.

Transscleral diode laser cyclophotocoagulation for refractory glaucoma secondary to juvenile idiopathic arthritis: a short term follow-up.

To evaluate the success rates of transscleral diode cyclophotocoagulation (TD-CPC) for refractory secondary glaucoma in a paediatric patient with juvenile idiopathic arthritis. Report of a case of a 6-year-old boy suffering from severe uveitis, and secondary open angle glaucoma. The patient had undergone bilateral cataract surgery, two prior trabeculectomies in the left and one in the right eye. He was under systemic immunomodulation with methotrexate and cyclosporine. He presented with medically uncontrolled glaucoma, with an intraocular pressure (IOP) of 36 and 34 mmHg in the right and left eye, respectively, under maximal medical antiglaucoma therapy. TD-CPC was performed under general anesthesia, including a total of 20 spots in the right and 34 in the left eye (2,000 mW, 2 s/spot) applied in one session. Visual acuity remained stable in the right eye and deteriorated in the left eye from 0.1 to no light perception. Postoperative hypotony was present 1 month post op and IOP was 14 mmHg in the left and 17 mmHg in the right eye, respectively, in the 6-month follow-up with a topical beta-blocker. The anterior chamber was quiet in both eyes. TD-CPC was effective in the short term as IOP lowering therapy in a pediatric patient with refractory uveitic glaucoma.