Follow-up of Mild Papilledema in Idiopathic Intracranial Hypertension with Optical Coherence Tomography

PURPOSE. To evaluate optical coherence tomography (OCT) measurement of peripapillary retinal nerve fiber layer (RNFL) thickness in patients with mild papilledema associated with idiopathic intracranial hypertension. METHODS. Patients with papilledema underwent a complete ophthalmic examination, including peripapillary RNFL analysis with OCT (Fast RNFL thickness 3.46; Carl Zeiss Meditec, Inc., Dublin, CA) at diagnosis and 3, 6, and 12 months after presentation. Age-and sex-matched control subjects underwent a similar evaluation. Changes in RNFL overall thickness and by quadrant and interocular differences were evaluated and studied regarding changes in visual field global indices (mean deviation [MD] and pattern SD [PSD]). RESULTS. Both eyes of 22 patients with mild papilledema and 22 control subjects were included. At diagnosis, the RNFL thickness was 183.3 Ϯ 74.7 m and 74.9% (78.5 m) greater than in control eyes. Mean RNFL thicknesses in all quadrants were significantly greater in eyes with papilledema (P ϭ 0.000). The mean average RNFL was significantly correlated with the MD ( ϭ Ϫ0.451, P ϭ 0.002) and PSD ( ϭ 0.370, P ϭ 0.013) at diagnosis. The RNFL thickness decreased significantly (P ϭ 0.000), whereas the mean MD and the mean PSD improved (P ϭ 0.000 and P ϭ 0.005, respectively) at each follow-up visit. Regression analysis showed that for every 10 m of mean RNFL thickness increase at baseline, there was a 0.6-dB decrease in MD at the last follow-up. CONCLUSIONS. Peripapillary RNFL thickness abnormalities assessed by OCT in patients with mild papilledema were quantitatively correlated with visual field sensitivity losses. The data support the possible use of OCT as a noninvasive quantitative method of monitoring the amount and evolution of papilledema. (Invest Ophthalmol Vis Sci

Diagnostic Accuracy of Nonmydriatic Fundus Photography for the Detection of Glaucoma in Diabetic Patients

Purpose. To determine the diagnostic accuracy for glaucoma of a set of criteria with nonmydriatic monoscopic fundus photography (NMFP) in diabetics. Methods. Diabetics recruited from a screening program for diabetic retinopathy and diabetic glaucoma patients recruited from our glaucoma unit were included. Any patient with evidence of diabetic retinopathy was excluded. Diabetic patients had to have no visual field defects to be included as controls. Glaucoma patients had to have a glaucomatous field defect in at least one eye to be included. One NMFP was taken per eye for all subjects. These photographs were evaluated by two masked glaucoma specialists for the presence of the following: bilateral cup to disc (C/D) ratio ≥0.6, notching or thinning of the neuroretinal rim, disc hemorrhages, and asymmetry in the C/D ratio between both eyes ≥0.2. This evaluation led to a dichotomous classification: if any of the above criteria was present, the patient was classified as glaucoma. If none were present, the patient was classified as normal. Results. 72 control subjects and 72 glaucoma patients were included. Evaluation of NMFP had a sensitivity of 79.17% and a specificity of 80.56% for specialist 1 and a sensitivity of 72.22% and a specificity of 88.88% for specialist 2 for the detection of glaucoma. The overall accuracy was 79.83% and 80.55%, respectively. Discussion. NMFP evaluation by a glaucoma specialist may be useful for the detection of glaucoma in diabetics

Bimatoprost/timolol fixed combination versus latanoprost in treatment-naïve glaucoma patients at high risk of progression: a pilot study.

Objective To compare a fixed combination of 0.03% bimatoprost and 0.5% timolol (BTFC) with latanoprost monotherapy (LM) in treatment-naïve patients with open-angle glaucoma (OAG) and risk factors for glaucomatous progression. Methods Patients were enrolled at 15 sites in Spain and Portugal, and were randomized 1:1 to BTFC or LM. Patients instilled one drop of medication once per day at 8 pm for 12 weeks. The primary outcome was change in intraocular pressure (IOP) at 12 weeks. Results Of 81 patients enrolled, 43 were randomized to BTFC and 38 to LM. Mean (SD) change in IOP from baseline to 12 weeks was significantly greater for BTFC than for LM: −13.5 mmHg (4.48) versus −11.4 mmHg (3.19), respectively (P=0.003). Similarly, at 12 weeks, significantly more BTFC patients than LM patients had IOP reductions of ≥40% (74.4% versus 47.4%, P=0.015) or ≥50% (46.5% versus 15.8%, P=0.003). Adverse events were more frequent with BTFC than with LM (33 versus 13 events), but most were mild in severity. The only serious adverse event (colon cancer) was adjudged unrelated to the study medication. Conclusion BTFC was effective and well tolerated in treatment-naïve patients with OAG at high risk of progressio

Real-world clinical experience with Idebenone in the treatment of Leber hereditary optic neuropathy

Background: Leber hereditary optic neuropathy (LHON) leads to bilateral central vision loss. In a clinical trial setting, idebenone has been shown to be safe and to provide a trend toward improved visual acuity, but long-term evidence of effectiveness in real-world clinical practice is sparse. Methods: Open-label, multicenter, retrospective, noncontrolled analysis of long-term visual acuity and safety in 111 LHON patients treated with idebenone (900 mg/day) in an expanded access program. Eligible patients had a confirmed mitochondrial DNA mutation and had experienced the onset of symptoms (most recent eye) within 1 year before enrollment. Data on visual acuity and adverse events were collected as per normal clinical practice. Efficacy was assessed as the proportion of patients with either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS) of visual acuity. In the case of CRR, time to and magnitude of recovery over the course of time were also assessed. Results: At time of analysis, 87 patients had provided longitudinal efficacy data. Average treatment duration was 25.6 months. CRR was observed in 46.0% of patients. Analysis of treatment effect by duration showed that the proportion of patients with recovery and the magnitude of recovery increased with treatment duration. Average gain in best-corrected visual acuity for responders was 0.72 logarithm of the minimal angle of resolution (logMAR), equivalent to more than 7 lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Furthermore, 50% of patients who had a visual acuity below 1.0 logMAR in at least one eye at initiation of treatment successfully maintained their vision below this threshold by last observation. Idebenone was well tolerated, with most adverse events classified as minor. Conclusions: These data demonstrate the benefit of idebenone treatment in recovering lost vision and maintaining good residual vision in a real-world setting. Together, these findings indicate that idebenone treatment should be initiated early and be maintained more than 24 months to maximize efficacy. Safety results were consistent with the known safety profile of idebenone

Parental Mosaicism in PAX6 Causes Intra-Familial Variability: Implications for Genetic Counseling of Congenital Aniridia and Microphthalmia

Mutations in PAX6 are involved in several developmental eye disorders. These disorders have considerable phenotypic variability, ranging from panocular forms of congenital aniridia and microphthalmia to isolated anomalies of the anterior or posterior segment. Here, we describe 3 families with variable inter-generational ocular expression of aniridia, iris coloboma, or microphthalmia, and an unusual transmission of PAX6 mutations from an unaffected or mildly affected parent; all of which raised suspicion of gonosomal mosaicism. We first identified two previously known nonsense mutations and one novel likely pathogenic missense variant in PAX6 in probands by means of targeted NGS. The subsequent segregation analysis by Sanger sequencing evidenced the presence of highly probable mosaic events in paternal blood samples. Mosaicism was further confirmed by droplet digital PCR analysis in several somatic tissues of mosaic fathers. Quantification of the mutant allele fraction in parental samples showed a marked deviation from 50%, with a range between 12 and 29% depending on cell type. Gonosomal mosaicsm was definitively confirmed in one of the families thanks to the availability of a sperm sample from the mosaic father. Thus, the recurrence risk in this family was estimated to be about one-third. This is the first report confirming parental PAX6 mosaicism as a cause of disease recurrence in aniridia and other related phenotypes. In addition, we demonstrated that post-zygotic mosaicism is a frequent and underestimated pathogenic mechanism in aniridia, explaining intra-familial phenotypic variability in many cases. Our findings may have substantial implications for genetic counseling in congenital aniridia. Thus, we also highlight the importance of comprehensive genetic screening of parents for new sporadic cases with aniridia or related developmental eye disease to more accurately assess recurrence risk. In conclusion, somatic and/or gonosomal mosaicism should be taken into consideration as a genetic factor to explain not only families with unaffected parents despite multiple affected children but also variable expressivity, apparent de novo cases, and even uncharacterized cases of aniridia and related developmental eye disorders, apparently lacking PAX6 mutations

Therapeutic benefit of idebenone in patients with Leber hereditary optic neuropathy: The LEROS nonrandomized controlled trial

Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to rapid and severe bilateral vision loss. Idebenone has been shown to be effective in stabilizing and restoring vision in patients treated within 1 year of onset of vision loss. The open-label, international, multicenter, natural history-controlled LEROS study (ClinicalTrials.gov NCT02774005) assesses the efficacy and safety of idebenone treatment (900 mg/day) in patients with LHON up to 5 years after symptom onset (N = 199) and over a treatment period of 24 months, compared to an external natural history control cohort (N = 372), matched by time since symptom onset. LEROS meets its primary endpoint and confirms the long-term efficacy of idebenone in the subacute/dynamic and chronic phases; the treatment effect varies depending on disease phase and the causative mtDNA mutation. The findings of the LEROS study will help guide the clinical management of patients with LHON

Sloan Digital Sky Survey IV: Mapping the Milky Way, Nearby Galaxies, and the Distant Universe

We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median $z\sim 0.03$). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between $z\sim 0.6$ and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July

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

Mapping the Structure-Function Relationship in Glaucoma and Healthy Patients Measured with Spectralis OCT and Humphrey Perimetry

Purpose. To study the structure-function relationship in glaucoma and healthy patients assessed with Spectralis OCT and Humphrey perimetry using new statistical approaches. Materials and Methods. Eighty-five eyes were prospectively selected and divided into 2 groups: glaucoma (44) and healthy patients (41). Three different statistical approaches were carried out: (1) factor analysis of the threshold sensitivities (dB) (automated perimetry) and the macular thickness (μm) (Spectralis OCT), subsequently applying Pearson’s correlation to the obtained regions, (2) nonparametric regression analysis relating the values in each pair of regions that showed significant correlation, and (3) nonparametric spatial regressions using three models designed for the purpose of this study. Results. In the glaucoma group, a map that relates structural and functional damage was drawn. The strongest correlation with visual fields was observed in the peripheral nasal region of both superior and inferior hemigrids (r=0.602 and r=0.458, resp.). The estimated functions obtained with the nonparametric regressions provided the mean sensitivity that corresponds to each given macular thickness. These functions allowed for accurate characterization of the structure-function relationship. Conclusions. Both maps and point-to-point functions obtained linking structure and function damage contribute to a better understanding of this relationship and may help in the future to improve glaucoma diagnosis

Current Approach in the Diagnosis and Management of Uveitic Glaucoma

Uveitic glaucoma (UG) typically is associated with very high intraocular pressure (IOP) and more intense optic nerve damage than other glaucoma types. This secondary glaucoma requires an early diagnosis and adequate management of both uveitis and glaucoma. It is mandatory to identify the mechanisms of IOP elevation that in many eyes have multiple combined mechanisms. Management of these patients commonly requires an interdisciplinary approach that includes a glaucoma specialist and rheumatologist to control the inflammation and IOP. Glaucoma surgery is required early in these patients due to the high IOP usually present and is less successful than in primary open-angle glaucoma. Recurrent uveitic episodes, multiple mechanism, and the complications associated with uveitis make surgical management of UG challenging. In this review, the management and treatment of UG are updated to clarify the pathogenesis and prevent optic nerve damage