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.

Binocular treatment for amblyopia: a systematic review.

PURPOSE: The treatment of unilateral amblyopia involves refractive adaptation, occlusion therapy or penalization with atropine drops. However, in recent years, the use of binocular digital therapy has shown promising results. Aim of this systematic review was to evaluate the effectiveness of binocular treatment of amblyopia compared with standard treatments or placebo therapy. METHODS: This systematic review was conducted in accordance to PRISMA statement. Electronic literature was thoroughly searched for articles published between 2013 and May 2024, in the following electronic database; Pubmed, CENTRAL, MedlinePlus, Medline Europe, PLOS, Scopus, Clinicaltrials.gov. The review comprised randomized control trials (RCTs) including patients with unilateral amblyopia, who received binocular therapy or standard amblyopia or placebo treatment for more than two weeks and who had visual acuity assessment pre- and post-treatment. Only articles written in English were included. Risk of bias was assessed with the Rob2 tool, while study quality was evaluated with the modified Jadad scale. RESULTS: Twenty RCTs, including 1769 patients, were incorporated into this systematic review. Twelve different types of binocular amblyopia treatments were identified and categorized into two main types. The first type involves the presentation of low-contrast images in the fellow eye, including stimuli presented only in the amblyopic eye. The second type combines this approach with complementary dichoptic deficits in the images presented to both eyes to encourage their simultaneous use. CONCLUSION: Binocular amblyopia treatment has shown promising results in addressing unilateral anisometropic, strabismic or mixed type of amblyopia. Nevertheless, further randomized controlled trials are essential to establish the exact dosage, type and duration of binocular therapy as a standard component of amblyopia care.

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 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.

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.

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.

Monkeypox-related ophthalmic disease (MPXROD): Monitoring the antiviral effect of tecovirimat with monkeypox virus detection in tear samples.

INTRODUCTION: Although monkeypox-related ophthalmic disease (MPXROD) is rare, visual impairing complications have been reported. At present, tecovirimat is the standard-of-care antiviral treatment. In this MPXROD case, the effect of tecovirimat was assessed with PCR analysis of tear samples and concurrent monitoring of inflammation with laser flare photometry (LFP). CASE DESCRIPTION: The patient presented with a palpebral lesion and a corneal ulcer in his right eye, with complete absence of the corneal epithelium, high intraocular pressure and anterior uveitis. MPXV-DNA was detected in tear samples with real-time PCR (RT-PCR). A total volume of 0.5 ml tear-wash was aspirated from the inferior fornix, following instillation of saline onto the ocular surface. In addition, LFP was used to quantify inflammation in both eyes. Viral load in tear samples was detected prior to treatment initiation. In the left eye, tear samples tested negative for MPXV-DNA one week post-treatment while MPXV-DNA was still detected in the right eye, before reaching undetectable levels four weeks post-treatment. Objective quantification of anterior chamber inflammation through LFP demonstrated gradual decrease that was more pronounced in the affected right eye and coincided with the clinical improvement of the corneal ulcer. CONCLUSIONS: This case of Mpox related corneal ulcer with associated uveitis manifests the feasibility of monitoring the antiviral effect of tecovirimat with virus detection in tear samples and LFP. Our observations indicate that tecovirimat resulted in viral load reduction in both eyes. RT-PCR MPXV detection in tear samples and LFP represent noninvasive tools that could assist with treatment response monitoring.

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.

OCT Angiography of the Retina and the Choroid in the Macula in Patients with Normal Tension Glaucoma and Primary Open Angle Glaucoma.

The aim of this study was to compare vessel density (VD) in the retina and choroid in eyes with primary open angle glaucoma (POAG), normal tension glaucoma (NTG) and controls. Patients with POAG, NTG and controls underwent OCT scanning of the macula and the disc followed by 6 × 6 mm macula OCT angiography (OCTA) imaging. Global and hemifield VD were recorded for the superficial (SVP) and deep (DVP) vascular plexus and the choriocapillaris (CC). The OCT thickness of the nerve fiber layer (NFL) and ganglion cell layer (GCC) was also measured. Data from 65 POAG, 33 NTG and 40 control eyes matched for age were analyzed. Mean SVP VD was lower in NTG and POAG eyes compared to controls (38.8 ± 5.3, 40.7 ± 6.8 and 48.5 ± 4.0%, p < 0.001). Mean DVP VD was lower in NTG and POAG eyes compared to controls (43.1 ± 6.1, 44.5 ± 7.6 and 48.6 ± 5.8%, p = 0.002). There was no difference in SVP VD or DVP VD between the glaucoma groups (p > 0.050). No difference was noted in CC VD between the groups (68.3 ± 2.3, 67.6 ± 3.7 and 68.5 ± 2.6%, p = 0.287). Lower SVP and DVP VD was seen in eyes with glaucoma compared to normal eyes. NTG and POAG eyes had similar VD loss. Eyes with glaucoma manifested similar CC VD compared to controls.

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.