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To describe a case of acute macular neuroretinopathy (AMN) in a patient with recent COVID-19 vaccination and infection who demonstrated atypical features on presentation.A 64-year-old woman presented with central vision loss in both eyes (OU). She had recently received the Moderna COVID-19 vaccine and rapidly developed systemic symptoms. Testing revealed COVID-19 infection. Visual acuities were 20/200 OU and near-infrared reflectance revealed hypo-reflective lesions in the maculae OU, optical coherence tomography (OCT) showed outer nuclear layer thinning and ellipsoid zone disruption OU, and OCT-angiography showed flow voids in the deep capillary plexus and choriocapillaris OU, all consistent with AMN. She was treated with oral prednisone with subsequent mild vision improvement and persistent scotomas.COVID-19 associated AMN can present with a more severe clinical presentation than classically seen in AMN. Ischemic and inflammatory changes due to COVID-19 infection may contribute to this more advanced presentation.

PURPOSE To quantitatively analyze and compare the novice vitreoretinal surgeons' performance after various types of external exposures. METHODS This prospective, self-controlled, cross-sectional study included 15 vitreoretinal fellows with less than 2 years of experience. Surgical performance was assessed using the Eyesi simulator after each exposure: Day 1, placebo, 2.5, and 5 mg/kg caffeine; Day 2, placebo, 0.2, and 0.6 mg/kg propranolol; Day 3, baseline simulation, breathalyzer reading of 0.06% to 0.10% and 0.11% to 0.15% blood alcohol concentration; Day 4, baseline simulation, push-up sets with 50% and 85% repetition maximum; Day 5, 3-hour sleep deprivation. Eyesi-generated total scores were the main outcome measured (0-700, worst to best). RESULTS Performances worsened after increasing alcohol exposure based on the total score (χ2 = 7; degrees of freedom = 2; P = 0.03). Blood alcohol concentration 0.06% to 0.10% and 0.11% to 0.15% was associated with diminished performance compared with improvements after propranolol 0.6 and 0.2 mg/kg, respectively (∆1 = -22 vs. ∆2 = +13; P = 0.02; ∆1 = -43 vs. ∆2 = +23; P = 0.01). Propranolol 0.6 mg/kg was positively associated with the total score, compared with deterioration after 2.5 mg/kg caffeine (∆1 = +7 vs. ∆2 = -13; P = 0.03). CONCLUSION Surgical performance diminished dose dependently after alcohol. Caffeine 2.5 mg/kg was negatively associated with dexterity, and performance improved after 0.2 mg/kg propranolol. No changes occurred after short-term exercise or acute 3-hour sleep deprivation.

Introduction: The aim of this study was to determine symptom-level risk factors for retinal tear/retinal detachment (RT/RD) in our patients presenting with symptoms of posterior vitreous detachment (PVD). Methods: We conducted a prospective cohort study of patients presenting to outpatient ophthalmology clinics at a single academic institution with complaint(s) of flashes, floaters, and/or subjective field loss (SFL). Patients received a standardized questionnaire regarding past ocular history and symptom characteristics including number, duration, and timing of flashes and floaters, prior to dilated ocular examination. Final diagnosis was categorized as RT/RD, PVD, ocular migraine, vitreous syneresis, or “other.” Simple and multivariate logistic regressions were used to identify symptoms predictive of various pathologies. Results: We recruited 237 patients (age 20–93 years) from March 2018 to March 2019. The most common diagnosis was PVD (141, 59.5%), followed by vitreous syneresis (38, 16.0%) and RT/RD (34, 14.3%). Of those with RT/RD, 16 (47.1%) had retinal tear and 15 (44.1%) had RD. Significant differences in demographic and examination-based factors were observed between these groups. Symptom-based predictive factors for RT/RD were the presence of subjective visual reduction (SVR; OR 2.77, p = 0.03) or SFL (OR 2.47, p = 0.04), and the absence of either floaters (OR 4.26, p = 0.04) or flashes (OR 2.95, p = 0.009). The number, duration, and timing of flashes and floaters did not predict the presence of RT/RD in our cohort. Within the RT/RD group, patients with RT were more likely to report floaters (100% vs. 66.7%, p = 0.018) and less likely to report SFL (0% vs. 86.7%, p < 0.001) compared to those with RD. Conclusion: While well-known demographic and exam-based risk factors for RT/RD exist in patients with PVD symptoms, the relative importance of symptom characteristics is less clear. We found that the presence of SVR and SFL, as well as the absence of either flashes or floaters, predicts RT/RD in patients with PVD symptoms. However, the number, duration, and timing of flashes and floaters may be less relevant in the triage of these patients.

Purpose Measurements of the ganglion cell complex (GCC), comprising the retinal nerve fiber (RNFL), ganglion cell, and inner plexiform layers, can be correlated with vision loss caused by optic nerve disease. Handheld optical coherence tomography (HH-OCT) can be used with sedation in children who are not amenable to traditional imaging. We report GCC and RNFL measurements in normal children using HH-OCT. Design Prospective observational study of normal children ≤5 years of age. Methods Healthy, full-term children ≤5 years of age undergoing sedation or anesthesia were enrolled. Exclusion criteria included prematurity and pre-existing neurologic, genetic, metabolic, or intraocular pathology. Demographic data, axial length (Master-Vu Sonomed Escalon, Lake Success, New York, USA), and HH-OCT macular and optic nerve volume scans at 0° (Bioptigen, Inc., Morrisville, North Carolina, USA) were obtained. Retinal segmentation was completed with DOCTRAP software, creating average volume thickness maps. Results Sixty-seven children (67 eyes, 31 males ranging in age from 3.4–70.9 months) were enrolled. Average axial length was 21.2 ± 1.0 mm with mean spherical equivalent +1.49 ± 1.34 diopters (range −2.25 to 4.25). Average GCC volume for the total retina was 0.28 ± 0.04 mm3. Forty-seven of these eyes had RNFL analysis. Average RNFL thickness of the papillomacular bundle was 38.2 ± 9.5 μm. There was no correlation between GCC volume, RNFL thickness, patient age, or axial length. Conclusion Average GCC volume and RNFL thickness was stable from 6 months to 5 years of age. This study provides normative data for GCC and RNFL obtained by HH-OCT in healthy eyes of young children, to serve in evaluating those with optic neuropathies.

Background/aimsFetal haemoglobin (HbF) has an oxyhaemoglobin dissociation curve that may affect systemic oxygenation and the development of retinopathy of prematurity (ROP). The study aim is to characterise the effects of HbF levels on systemic oxygenation and ROP development.MethodsProspective study conducted from 1 September 2017 through 31 December 2018 at the Johns Hopkins NICU. Preterm infants with HbF measured at birth, 31, 34 and 37 weeks post-menstrual age (PMA), complete blood gas and SpO2recorded up to 42 weeks PMA, and at least one ROP exam were included.ResultsSixty-four preterm infants were enrolled. Higher HbF was associated with significantly higher SpO2, lower PCO2, lower FiO2from birth to 31 weeks PMA and 31 to 34 weeks PMA (rs=0.51, rs=−0.62 and rs=−0.63; ps=0.71, rs=−0.58 and rs=−0.79; p2was required for HbF in the lowest tercile from birth compared with HbF in the highest tercile to 31 weeks and 31 to 34 weeks PMA; FiO2=35 (21–100) versus 21 (21–30) p2=30 (28–100) versus 21 (21–30) p2, and lower levels of HbF (pConclusionLow HbF levels correlated with poor oxygenation indices and increased risk for ROP. O2saturation goals to prevent ROP may need to incorporate relative amount of HbF.

Objectives/hypothesis To evaluate the trend and factors associated with surgical management of orbital cellulitis. Study design Retrospective database study. Methods Study using the State Inpatient Databases (SIDs) from 2008 to 2015. Patients with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code for orbital cellulitis were identified in the SIDs for the following states: Arkansas, Florida, Iowa, Maryland, Nebraska, New York, and Wisconsin. Surgery was defined as an ICD-9-CM procedure code for orbitotomy and/or functional endoscopic sinus surgery. The trend of surgery over time was evaluated using the Cochran-Armitage test. Multivariable logistic regression models were used to identify patient- and hospital-level factors associated with surgery. Results From 2008 to 2013, the number of hospitalizations for orbital cellulitis ranged from 1,349 to 1,574, but declined to 865 in 2014. From 2008 to 2015, the number of surgeries ranged from 103 to 154. For children (n = 3,041), age, ophthalmologic comorbidity, and conjunctival edema were significantly associated with surgery, whereas for adults (n = 7,961), male gender, private insurance, optic neuritis, and cranial nerves III/VI/VI palsy were associated with surgery. Conclusions Although the number of inpatient hospitalizations for orbital cellulitis has markedly declined, the number of surgeries for orbital cellulitis has remained fairly stable, leading to an observed higher proportion of hospitalized patients undergoing surgery. Future directions include extending the time frame to the present day to assess current rates of hospitalization and surgery. Knowledge of surgical trends and patient- and hospital-level characteristics associated with surgery may help improve management guidelines for and understanding of this vision-threatening disease. Level of evidence NA Laryngoscope, 130:567-574, 2020.

We conducted a case-control study using the Eyesi simulator to assess the surgical performance of 24 chronic cocaine users (CCUs) and 24 sex-/age-matched controls to numerically quantify ophthalmic microsurgical simulator performance and fine motor deficiencies. The inclusion criteria were no exposure to illicit drugs other than cocaine, marijuana, or alcohol within the previous month and no health conditions that could impact manual task performance. The outcomes included surgical scores (0–100, worst-best) and task completion time (minutes). Fisher's exact test, analysis of variance, Mann-Whitney U test, and Kruskal-Wallis test followed by Dunn-Bonferroni post-hoc were conducted for statistical analysis. The Eyesi scores were lower among CCUs compared to controls for bimanual tasks (4.50 ± 14.30 vs. 18.46 ± 26.64, p = 0.012), for exercises demanding upper and lower limb coordination (both hands and two foot pedals, respectively) (74.13 ± 35.01 vs. 85.21 ± 24.1, p = 0.045), and in the overall score for all three tasks (27.38 ± 15.06 vs. 39.5 ± 18.66, p = 0.021). CCUs took longer to complete tasks when performing exercises demanding upper and lower limb coordination compared to controls (1.26 ± 0.38 vs. 1.02 ± 0.44 min, p = 0.006). Individuals who used cocaine during the previous month had an independent lower bimanual score compared to controls (1.42 ± 4.91 vs. 18.46 ± 26.64, p = 0.018). No differences in performance among the CCUs were attributable to sporadic cannabis or alcohol use. Chronic use of cocaine negatively impacted fine dexterity as measured by bimanual tasks or maneuvers that required simultaneous coordination of the upper and lower limbs. This was most notable among individuals who used cocaine during the 1-month period before the simulation.

IMPORTANCE: Vitreoretinal surgery can be technically challenging and is limited by physiologic characteristics of the surgeon. Factors that improve accuracy and precision of the vitreoretinal surgeon are invaluable to surgical performance. OBJECTIVES: To establish weight-adjusted cutoffs for caffeine and β-blocker (propranolol) intake and to determine their interactions in association with the performance of novice vitreoretinal microsurgeons. DESIGN, SETTINGS, AND PARTICIPANTS: This single-blind cross-sectional study of 15 vitreoretinal surgeons who had less than 2 years of surgical experience was conducted from September 19, 2018, to September 25, 2019, at a dry-laboratory setting. Five simulations were performed daily for 2 days. On day 1, performance was assessed after sequential exposure to placebo, low-dose caffeine (2.5 mg/kg), high-dose caffeine (5.0 mg/kg), and high-dose propranolol (0.6 mg/kg). On day 2, performance was assessed after sequential exposure to placebo, low-dose propranolol (0.2 mg/kg), high-dose propranolol (0.6 mg/kg), and high-dose caffeine (5.0 mg/kg). INTERVENTIONS: Surgical simulation tasks were repeated 30 minutes after masked ingestion of placebo, caffeine, or propranolol pills during the 2 days. MAIN OUTCOMES AND MEASURES: An Eyesi surgical simulator was used to assess surgical performance, which included surgical score (range, 0 [worst] to 700 [best]), task completion time, intraocular trajectory, and tremor rate (range, 0 [worst] to 100 [best]). The nonparametric Friedman test followed by Dunn-Bonferroni post hoc test was applied for multiple comparisons. RESULTS: Of 15 vitreoretinal surgeons, 9 (60%) were male, with a mean (SD) age of 29.6 (1.4) years and mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) of 23.15 (2.9). Compared with low-dose propranolol, low-dose caffeine was associated with a worse total surgical score (557.0 vs 617.0; difference, –53.0; 95% CI, –99.3 to –6.7; P = .009), a lower antitremor maneuver score (55.0 vs 75.0; difference, –12.0; 95% CI, –21.2 to –2.8; P = .009), longer intraocular trajectory (2298.6 vs 2080.7 mm; difference, 179.3 mm; 95% CI, 1.2-357.3 mm; P = .048), and increased task completion time (14.9 minutes vs 12.7 minutes; difference, 2.3 minutes; 95% CI, 0.8-3.8 minutes; P = .048). Postcaffeine treatment with propranolol was associated with performance improvement; however, surgical performance remained inferior compared with low-dose propranolol alone for total surgical score (570.0 vs 617.0; difference, –51.0; 95% CI, –77.6 to –24.4; P = .01), tremor-specific score (50.0 vs 75.0; difference, –16.0; 95% CI, –31.8 to –0.2; P = .03), and intraocular trajectory (2265.9 mm vs 2080.7 mm; difference, 166.8 mm; 95% CI, 64.1-269.6 mm; P = .03). CONCLUSIONS AND RELEVANCE: The findings suggest that performance of novice vitreoretinal surgeons was worse after receiving low-dose caffeine alone but improved after receiving low-dose propranolol alone. Their performance after receiving propranolol alone was better than after the combination of propranolol and caffeine. These results may be helpful for novice vitreoretinal surgeons to improve microsurgical performance.

Retinal arterial macroaneurysm (RAM) was first published in a report by Loring in 1880 in which he described a bulging ectasia of the inferotemporal retinal artery in an asymptomatic healthy 25-year-old man (Loring 1880). Fernandez made the first association of retinal artery macroaneurysm with systemic hypertension in 1920 (Fernandez 1920). Robertson was the first to define retinal artery macroaneurysm as a distinct clinical entity and its natural history in 1973 (Robertson 1973). RAM most commonly affects women in their 60s and 70s and is associated with hypertension and atherosclerotic vessel disease. RAM is usually unilateral but may be bilateral in 10% of cases (Rabb et al. 1988). They are usually single but may be multiple in 20% of cases (Rabb et al. 1988).

Precision medicine refers to a stratification of patients using a wide array of individual-specific data to enable precise targeting of disease subgroups with the best available diagnostic and therapeutic approaches. Within ophthalmology, this strategy is being applied successfully and is most evident in the management of the inherited diseases. This paradigm shift in provision of care is accelerated by the emergence of novel imaging technologies, robotics, and artificial intelligence, as well as emerging technologies that integrate bioinformatics data into clinically relevant knowledge. This knowledge is used in turn to develop a system capable of supporting clinical decision-making and utilization of high-precision therapeutic options in both a personalized and cost-effective way. Examples of the diverse areas making rapid progress toward full implementation of precision medicine include, but are not limited to, ocular genetic diseases, robotic surgery, virtual reality simulations, modern imaging techniques, and the role of healthcare providers.

Fulminant idiopathic intracranial hypertension (FIIH) is a subtype of idiopathic intracranial hypertension (IIH) characterized by rapid, severe, progressive vision loss. Surgical intervention is often performed either as a cerebrospinal fluid (CSF) shunt procedure or an optic nerve sheath fenestration or, at times, both. These surgical procedures carry a significant risk of morbidity and failure. We present 2 patients in whom a temporary lumbar drain was successfully used in the management of medically undertreated pediatric FIIH, and circumvented the need for surgical intervention.

Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly in developed countries. Current treatment options are limited and only appropriate for some cases. Since environmental factors are directly involved in AMD pathogenesis, increasing research is focused on prevention as a primary AMD treatment strategy. Therefore, the identification and modification of risk factors has the potential to reduce morbidity. Prior work explores the association between dietary habits, nutritional supplementation, and AMD risk, showing that “healthy” and low-fat meals may be strategies to lower the chance of developing the disease. This hypothesis has been extended to suggest that some cholesterol-lowering drugs, such as statins, might act as a protective agent. However, a role for statins in AMD remains controversial in the literature.

PurposeTo investigate the effect of prior intravitreal injections on intraoperative and postoperative complication rates associated with cataract surgery.MethodsA retrospective cohort analysis reviewed 10 105 cataract surgery procedures performed by experienced surgeons at the Duke Eye Center from 1 January 2005 to 10 December 2012. A group of 197 eyes with prior intravitreal injections was compared with an equal number of matched control eyes without prior injection using the Fisher's exact test of difference in proportions and the Wilcoxon rank-sum test of difference in means. Outcomes analyzed included baseline demographic information, preoperative clinical characteristics, prevalence of intraoperative complications, and postoperative intraocular pressure, glaucoma surgery, and glaucoma medication requirement through 1 year following cataract surgery.ResultsAn increased rate of intraoperative complications was identified during cataract surgery in eyes with prior intravitreal injections compared with control eyes (3 vs 0%, P=0.030). Injection eyes required more glaucoma medications at 1 year, but no difference was identified if steroid injections were excluded. No difference in postoperative IOP or glaucoma surgery was identified. No cases of endophthalmitis were reported.ConclusionsA history of intravitreal injections may be a risk factor for cataract surgery-related intraoperative complications. We hypothesize this may be due to unidentified iatrogenic lens trauma during intravitreal injections. Particular attention to the posterior capsule during preoperative assessment and intraoperatively is recommended in eyes undergoing cataract surgery with a prior history of intravitreal injections.

Endodermal cysts, also known as neurogenic, neuroenteric, foregut, bronchogenic, respiratory, epithelial, teratomatous, or gastrocytoma cysts, can be found in the central nervous system, predominantly in the subarachnoid space of the cervical and thoracic spinal cord. We describe a child with an endodermal cyst of the third nerve and highlight neuroimaging findings, pathological correlation, clinical course, and patient management.

A 57-year-old white woman developed autoimmune retinopathy (AIR) in both eyes associated with bilateral autoimmune sensorineural hearing loss. Laboratory testing was positive for 68kDa (heat-shock protein) and 136kDa (human interstitial retinoid-binding protein). Extensive cancer screening was negative. Spectral-domain optical coherence tomography enhanced depth imaging demonstrated a markedly thickened choroid in both eyes. En face imaging showed a distinctive pattern of granular hyperreflective foveal dots. The concurrent sensorineural hearing loss was thought to be of autoimmune origin and also responded to immunosuppressive treatment. Eyes with non-paraneoplastic, seropositive AIR may have associated increased choroidal thickness. Audiology testing should be considered. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:362–365.]

Recent Spectralis (Heidelberg, Germany) spectral domain optical coherence tomography (SD-OCT) research software can automatically quantify the thickness of each individual retinal layer. The macular ganglion cell layer (GCL) and ganglion cell complex may be more sensitive for detecting glaucoma than the peripapillary retinal nerve fiber layer (pRNFL). The aim of this study was to characterize and compare the volume of each macular layer in the eyes of children with glaucoma versus those of normal controls.The medical records of children with primary glaucoma and physiologic cupping who had undergone Spectralis SD-OCT imaging of the macula and pRNFL were reviewed retrospectively. Controls were recruited from a separate prospective study. Children with refractive error of±5 or retinal or neurologic abnormalities were excluded. The average volume of each of the 8 retinal layers in the macula (central 6 mm) and pRNFL were compared among diagnostic groups.A total of 80 eyes of 80 children were included: 37 glaucoma eyes (25 with primary congenital and 12 with juvenile open-angle glaucoma) and 43 nonglaucoma eyes (28 with physiologic cupping). Eyes with glaucoma had significantly thinner mean macular nerve fiber layers, ganglion cell layers, inner plexiform layers, and pRNFLs than nonglaucomatous eyes: 0.82 ± 0.24 μm versus 1.00 ± 0.12 μm; 0.93 ± 0.22 μm versus 1.13 ± 0.10 μm; 0.80 ± 0.14 μm versus 0.91 ± 0.07 μm; 81.6 ± 26.5 μm versus 102.7 ± 10.0 μm, respectively (P 0.00556 for all). Eyes without cupping and those with physiologic cupping were equivalent for all variables tested.Children with glaucoma have thinning of the three innermost retinal macular layers.

Purpose Hematogenous dissemination of fungus of the eyes can manifest as chorioretinitis or endophthalmitis. Early reports of this condition describe the prevalence to range from 10% to 40%; however, more recent studies have suggested a declining prevalence, presumably because of widespread use of prophylactic antifungal therapy and earlier diagnosis and treatment of systemic illness before ocular symptoms become apparent. This study estimates the current prevalence and microbial profile of fungal chorioretinitis and endophthalmitis among patients with positive fungal cultures at a tertiary care medical center. Design Retrospective case series. Participants A total of 211 adult and pediatric inpatients with fungemia. Methods All inpatient consultations at our institution to evaluate for ocular involvement by fungal organisms from June 3, 2006, to September 3, 2009, were reviewed. Main Outcome Measures The presence or absence of ocular lesions consistent with disseminated fungus. Results A total of 211 patients (83 pediatric, 128 adult) had consult requests indicating concern for ocular fungal infection. More than 97% of these patients had at least 1 positive fungal culture. In decreasing order of frequency, the organisms identified were Candida albicans , C. parapsilosis, C. glabrata, C. tropicalis , and others. More than 98% of all patients were receiving systemic antifungal therapy (average duration 6.5 days) at the time of examination. No pediatric patients and only 2 adult patients had positive findings (i.e., chorioretinitis or endophthalmitis); 1 of these 2 patients was able to verbalize symptoms and reported floaters and blurring, whereas the other patient was unable to verbalize. Visual symptoms were rare (3.5%) among patients with negative findings who could verbalize visual symptoms. Three adults had nonspecific fundus lesions that were considered inconsistent with chorioretinitis. Conclusions Disseminated ocular fungal infection is rare in the current era of widespread prophylactic antifungal therapy. Less than 1% of patients in our study had ocular involvement from fungus, and no patients who were asymptomatic had involvement. We suggest that routine ophthalmic consultation on fungemic inpatients is not an efficient use of clinical resources; however, validation of these findings via a prospective study is desired. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Purpose To evaluate the effect of vitrectomy on intraocular pressure (IOP). Methods Retrospective cohort study. Medical records of 101 eyes of 101 patients undergoing nonemergent vitrectomy were reviewed for rates of open-angle glaucoma, increased IOP of >4 mmHg from baseline, change in IOP from baseline, and cataract formation. Preoperative and last measured IOPs were recorded. Baseline risk characteristics including lens status and diabetes were analyzed. Main outcome measures were 1) incidence of open-angle glaucoma; 2) increase in IOP of >4 mmHg; and 3) change in IOP. Results Mean follow-up was 49 months (range, 12-105 months). Mean baseline IOP was 15.3 mmHg, and mean final IOP was 15.8 mmHg (P = 0.3). At the most recent examination, 35 study eyes had a decrease in IOP from baseline, while 14 eyes had no change and 52 eyes had an increase in IOP. Four study eyes were newly diagnosed with ocular hypertension. No study eye developed open-angle glaucoma or required medical, laser, or surgical treatment for glaucoma. Incidence of increased IOP of >4 was 7% at 4 years and 34% at 8 years. Subgroup analysis of 66 patients comparing study eyes with nonvitrectomized fellow eyes demonstrated no significant difference in rates of increased IOP of >4 (P = 0.85). Neither diabetes nor pseudophakia was associated with significantly increased IOP. Conclusion In this series, vitrectomy does not appear to increase IOP even after removal of the crystalline lens.

To evaluate the effect of previous vitrectomy on the incidence of macular oedema (MO) after cataract surgery in diabetic eyes.Ninety phakic eyes of 70 patients with diabetes undergoing non-emergent vitrectomy surgery were reviewed for rates of postvitrectomy MO, cataract formation and postcataract surgery MO. Preoperative and final best-corrected visual acuity were recorded. Baseline risk characteristics were analysed.Postvitrectomy MO increases initially but then levels off at 28% by 4 years. Cumulative proportion of eyes requiring cataract surgery after vitrectomy climbs steadily, reaching 40% at 4 years and 60% at 8 years. Of those eyes which underwent vitrectomy and then subsequent cataract surgery, the incidence of postvitrectomy MO was 6% at 6 months, and that of postcataract surgery MO was 30% at 6 months (p0.02). Previous clinically significant macular oedema (CSMO) predicted development of postcataract surgery MO (p0.04).Previous vitrectomy does not appear to lessen rates of postcataract surgery MO. Cataract formation is common after vitrectomy in diabetic eyes, and risk of postcataract surgery MO is substantial and more likely in eyes with prior CSMO. Cataract formation and risk of postcataract surgery MO should be considered when assessing the long-term benefits of vitrectomy surgery in patients with diabetes.

Background— We and others have reported mutations in the cardiac predominant sodium channel gene SCN5A in patients with atrial fibrillation (AF). We also have reported that SCN1B is associated with Brugada syndrome and isolated cardiac conduction disease. We tested the hypothesis that mutations in the 4 sodium channel β-subunit genes SCN1B – SCN4B contribute to AF susceptibility. Methods and Results— Screening for mutations in the 4 β-subunit genes was performed in 480 patients with AF (118 patients with lone AF and 362 patients with AF and cardiovascular disease) and 548 control subjects (188 ethnically defined anonymized subjects and 360 subjects without AF). The effects of mutant β-subunits on SCN5A mediated currents were studied using electrophysiological studies. We identified 2 nonsynonymous variants in SCN1B (resulting in R85H, D153N) and 2 in SCN2B (R28Q, R28W) in patients with AF. These occur at residues highly conserved across mammals and were absent in control subjects. In 3 of 4 mutation carriers, the ECGs showed saddleback-type ST-segment elevation in the right precordial leads. Transcripts encoding both SCN1B and SCN2B were detected in human atrium and ventricle. In heterologous expression studies using Chinese hamster ovary cells, the mutant β1- or β2-subunits reduced SCN5A -mediated current and altered channel gating compared with coexpression of wild-type subunits. Conclusions— Loss of function mutations in sodium channel β-subunits were identified in patients with AF and were associated with a distinctive ECG phenotype. These findings further support the hypothesis that decreased sodium current enhances AF susceptibility.

To describe the incidence and significance of retinal changes in pediatric eyes with glaucoma and nonglaucomatous optic atrophy by optical coherence tomography (OCT).Retrospective observational case series.OCT scans performed on children with either glaucoma or nonglaucomatous optic atrophy were retrospectively reviewed. Excluded were poor-quality scans and diagnoses of ocular hypertension or glaucoma suspects.Included were 227 eyes (227 children), 151 with glaucoma and 76 with nonglaucomatous optic atrophy. Outer retinal changes were present in 20 of 151 glaucoma eyes (13.2%) (12 prior intraocular surgery, 5 uveitis, 3 primary retinopathy) and 6 of 76 nonglaucomatous optic atrophy eyes (7.9%) (1 retinal vasculitis, 3 papilledema, 2 infiltrative optic neuropathy). Excluding eyes with outer retinal changes, isolated inner nuclear layer (INL) cysts were found in 6 of 131 eyes with glaucoma (4.6%) (3 uveitis, 1 prior hydrocephalus, 1 uveitis and pars plana vitrectomy, and 1 juvenile open-angle glaucoma) and 21 of 70 eyes with nonglaucomatous optic atrophy (30%) (5 optic neuritis, 11 anterior visual pathway tumors, 2 papilledema, 3 other) (P.0001). Compared to eyes without INL cysts, those with INL cysts had thinner average retinal nerve fiber layer (RNFL) (78.2 ± 1.8 μm vs 52.0 ± 4.8 μm, P.0001) and worse vision (logMAR = 0.33 ± 0.04 vs 0.65 ± 0.09, P.002).INL cysts are more frequent in pediatric nonglaucomatous optic atrophy than glaucoma; they are associated with worse vision and thinner RNFL. Outer retinal changes were exclusively seen in pathology that directly affected the retina. In children, INL cysts and/or outer retinal changes without prior history of intraocular surgery or uveitis should prompt further evaluation.

Nitric oxide (NO) regulates vascular smooth muscle cell (VSMC) structure and function, in part by activating soluble guanylate cyclase (sGC) to synthesize cGMP. The objective of this study was to further characterize the signaling mechanisms by which NO regulates VSMC gene expression using transcription profiling. DNA microarrays were hybridized with RNA extracted from rat pulmonary artery smooth muscle cells (RPaSMC) exposed to the NO donor compound, S-nitroso-glutathione (GSNO). Many of the genes, whose expression was induced by GSNO, contain a cAMP-response element (CRE), of which one encoded the inducible cAMP early repressor (ICER). sGC and cAMP-dependent protein kinase, but not cGMP-dependent protein kinase, were required for NO-mediated phosphorylation of CRE-binding protein (CREB) and induction of ICER gene expression. Expression of a dominant-negative CREB in RPaSMC prevented the NO-mediated induction of CRE-dependent gene transcription and ICER gene expression. Pre-treatment of RPaSMC with the intracellular calcium (Ca(2+)) chelator, BAPTA-AM, blocked the induction of ICER gene expression by GSNO. The store-operated Ca(2+) channel inhibitors, 2-ABP, and SKF-96365, reduced the GSNO-mediated increase in ICER mRNA levels, while 2-ABP did not inhibit GSNO-induced CREB phosphorylation. Our results suggest that induction of ICER gene expression by NO requires both CREB phosphorylation and Ca(2+) signaling. Transcription profiling of RPaSMC exposed to GSNO revealed important roles for sGC, PKA, CREB, and Ca(2+) in the regulation of gene expression by NO. The induction of ICER in GSNO-treated RPaSMC highlights a novel cross-talk mechanism between cGMP and cAMP signaling pathways.

Background: We have recently reported mutations in the cardiac sodium channel gene SCN5A in 5.9% of patients with atrial fibrillation (AF). In this study, we tested the hypothesis that mutations in sodium channel β subunit genes SCN1B-4B contribute to AF susceptibility. Methods and results: All 4 βsubunit genes were resequenced in 376 patients with AF (118 patients with lone AF and 258 patients with AF and cardiovascular disease) and 188 ethnically-defined controls. We identified 2 non-synonymous variants in SCN1B (resulting in R85H, D153N) and 2 in SCN2B (R28Q, R28W) in patients with AF; these occur at residues highly conserved across mammals and were absent in controls. In 3 of 4 mutation carriers, there was saddle back type ST-segment elevation in the right precordial leads of electrocardiogram. Transcripts encoding both SCN1B and SCN2B were detected in human atrium and ventricle. To assess function in vitro , CHO cells were transfected with SCN5A without β subunit, SCN5A with wild-type (WT) β subunit, or SCN5A with mutant β subunit: all 4 mutants altered SCN5A current to a variable extent compared to WT β subunits. WT β1 increased SCN5A currents by 75%, and induced a negative shift in steady-state activation (−10.2 mV) and inactivation (−6.7 mV), compared to SCN5A alone. D153N β1 caused partial loss of function, with increased SCN5A current but to a smaller extent (24%) than WT β1, and a negative shift in steady-state activation (−12.1 mV) and inactivation (−8.1 mV) similar to WT. R85H β1 produced a pure loss of function, with currents no different from SCN5A alone. WT β2 did not change SCN5A current amplitude, while R28Q β2 and R28W β2 decreased current by 36% and 30%, respectively; and positively shifted steady-state activation by +7.4 mV and +5.1 mV, respectively, compared to WT. Conclusion: Loss of function mutations in sodium channel β subunits were identified in patients with AF, and were associated with a distinctive ECG phenotype. These findings further support the hypothesis that decreased sodium current enhances AF susceptibility.