LONG-TERM USE OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: Although pivotal trials have demonstrated efficacy of anti-vascular endothelial growth factor therapy in neovascular age-related macular degeneration, there is a paucity of clinical data about the long-term (>5 years) treatment. METHODS: Retrospective analysis of all patients with neovascular age-related macular degeneration who were actively treated, had received >40 anti-vascular endothelial growth factor injections, and were followed for ≥5 years. Snellen-corrected visual acuity, initial drug choice, and times elapsed between treatments were collected. Rates of endophthalmitis and outcomes of submacular hemorrhage were also evaluated. RESULTS: A total of 88 patients (162 eyes) met the inclusion criteria: the average patient age was 86.3 years with an average follow-up period of 7.6 years. The average total number of injections per eye was 69 (18.0 SD); a total of 11,208 injections were given throughout the study period, and 6 cases (0.05%) of endophthalmitis were observed. Overall, there was a clinical and statistical difference in average Snellen-corrected visual acuity at Injections #2,#3, #4, #5, #6, #10, and #20, as compared with baseline ( P = 0.03, P < 0.01, P = 0.02, P < 0.01, P = 0.01, P = 0.01, P < 0.01, respectively). Patients in the Snellen-corrected visual acuity subgroup 20/20 to 20/40 maintained vision until injection #30. Seven eyes experienced a visually significant submacular hemorrhage. CONCLUSION: This neovascular age-related macular degeneration cohort received on average eight anti-vascular endothelial growth factor injections per year for approximately 8 years; eyes with good (≥20/40) initial baseline vision maintained their visual acuity, whereas those with worse Snellen-corrected visual acuity (≤20/50) had a robust initial improvement that diminished with time. Most patients were maintained on the same initial drug of choice and the rate of endophthalmitis was low.

Characteristics of bradyarrhythmia in patients with COVID-19: Systematic scoping review.

COVID-19 has recently been associated with the development of bradyarrhythmias, although its mechanism is still unclear. We aim to summarize the existing evidence regarding bradyarrhythmia in COVID-19 and provide future directions for research. Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including"Bradycardia," "atrioventricular block," and "COVID-19″ from their inception to October 13, 2021. Forty-three articles, including 11 observational studies and 59 cases from case reports and series, were included in the systematic review. Although some observational studies reported increased mortality in those with bradyarrhythmia and COVID-19, the lack of comparative groups and small sample sizes hinder the ability to draw definitive conclusions. Among 59 COVID-19 patients with bradycardia from case reports and series, bradycardia most often occurred in those with severe or critical COVID-19, and complete heart block occurred in the majority of cases despite preserved LVEF (55.9%). Pacemaker insertion was required in 76.3% of the patients, most of which were permanent implants (45.8%). This systematic review summarizes the current evidence and characteristics of bradyarrhythmia in patients with COVID-19. Further studies are critical to assess the reversibility of bradyarrhythmia in COVID-19 patients and to clarify potential therapeutic targets including the need for permanent pacing.

LONG-TERM VISUAL OUTCOMES AND THE TIMING OF SURGICAL REPAIR OF FOVEA-SPLITTING RHEGMATOGENOUS RETINAL DETACHMENTS.

PURPOSE: To evaluate the visual outcomes and the affect of timing of surgical repair of fovea-splitting rhegmatogenous retinal detachments. METHOD: A retrospective, consecutive cohort from multiple surgeons at a single center. Fovea status (fovea-on, fovea-splitting, or fovea-off) was classified by preoperative optical coherence tomography. The primary outcome measure was the visual acuity at the last follow-up that was further correlated with the timing of surgical repair. RESULTS: One hundred and ninety-five eyes were included with 62 fovea-on, 65 fovea-splitting, and 68 fovea-off detachments. The mean preoperative logarithm of the minimum angle of resolution visual acuity for fovea-on, fovea-splitting, and fovea-off groups was 0.16 ± 0.21, 0.70 ± 0.56, and 1.67 ± 0.87, respectively (P = <0.001). Mean postoperative logarithm of the minimum angle of resolution visual acuity for fovea-on, fovea-splitting, and fovea-off groups were 0.07 ± 0.13, 0.10 ± 0.15, and 0.20 ± 0.22, respectively (P = <0.001). A statistically significant difference in mean postoperative logMAR visual acuity was found between fovea-off and fovea-on groups (P = 0.003) and between fovea-off and fovea-splitting groups (P = 0.013), however not between fovea-on and fovea-splitting groups (P = 0.827). Visual acuity improved when repair was performed earlier after presentation for fovea-on (R = 0.378, P = 0.002) and fovea-off groups (R = 0.277, P = 0.022), but not for the fovea-splitting group (R = 0.089, P = 0.481). CONCLUSION: We described the favorable visual outcomes of surgery for fovea-splitting rhegmatogenous retinal detachment and correlated these with the timing of surgical repair, which may help guide the management of this urgent, vision-threatening condition.

PERIPHERAL RETINAL ANGIOGRAPHIC FINDINGS IN MACULAR TELANGIECTASIS TYPE 2.

PURPOSE: To evaluate the retinal periphery in patients with idiopathic juxtafoveal telangiectasis or macular telangiectasis Type 2 (MacTel2), using widefield fluorescein angiography. METHODS: Single-center, retrospective, observational case series of 50 eyes of 50 patients with MacTel2 and 50 eyes of 50 age-matched controls. RESULTS: Thirty-seven eyes in the MacTel2 group (74%) showed peripheral capillary nonperfusion or dropout, compared with 37 eyes in the control group (74%, P = 1.0). Morphologically, the MacTel2 group trended toward having a higher proportion of pruning-type capillary dropout (44%) compared with controls (28%), but this was not statistically significant (P = 0.12). Patients with MacTel2 had a higher incidence of microaneurysms compared with controls (MacTel2 56%; controls 42%; P = 0.048), independent of age or systemic risk factors. There was no difference in the incidence of venous-venous shunts (MacTel2 10%; controls 10%; P = 1.0), arteriovenous shunts (MacTel2 14%; controls 18%; P = 0.60), venous tortuosity (MacTel2 60%; controls 66%; P = 0.58), or arterial tortuosity (MacTel2 54%; controls 68%; P = 0.20), which was mild in most cases. CONCLUSION: We note a high incidence of peripheral vascular and retinal findings in both patients with MacTel2 and age-matched controls, using widefield fluorescein angiography. Patients with MacTel2 had significantly more microaneurysms, independent of age or other systemic risk factors.

CLINICAL OUTCOMES AND TREATMENT COURSE OF EYES WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION FOLLOWING THE DEVELOPMENT OF ENDOPHTHALMITIS.

PURPOSE: To evaluate the clinical course of patients with neovascular age-related macular degeneration (nAMD) after developing endophthalmitis during their treatment with intravitreal injections. METHODS: Multicenter, retrospective series. RESULTS: From April 2013 to October 2018, 196,598 intravitreal anti-vascular endothelial growth factor (VEGF) injections were performed, with 75 cases of endophthalmitis (incidence 0.0381%). There was no association between intravitreal anti-VEGF drug (P = 0.29), anesthetic method (P = 0.26), povidone concentration (P = 0.22), or any intraprocedure variable and endophthalmitis incidence. Seventy-two patients (96%) were treated with intravitreal tap and inject , while 3 underwent immediate pars plana vitrectomy. After endophthalmitis resolution, 17 patients (22.7%) were not re-treated for nAMD (in 10 cases due to inactive disease; follow-up, 115 ± 8.4 weeks). Patients required less frequent anti-VEGF injections after infection (7.4 ± 0.61 weeks vs. 11.5 ± 1.8 weeks; P = 0.004). Preinfection logarithm of the minimum angle of resolution visual acuity was 0.585 ± 0.053 (∼20/77). It worsened with endophthalmitis (1.67 ± 0.08, ∼20/935; P < 0.001) and again on postendophthalmitis treatment day 1 (1.94 ± 0.064; count fingers; P < 0.001), but improved after reinitiating nAMD therapy (1.02 ± 0.11; ∼20/209; P < 0.001). Better visual acuity on postendophthalmitis week 1 (P = 0.002) and reinitiation of nAMD treatment (P = 0.008) were associated with better final visual acuity, and streptococcal culture with worse visual acuity (P = 0.028). The postendophthalmitis treatment interval was associated with the anti-VEGF drug used (aflibercept = ranibizumab > bevacizumab; P < 0.001). CONCLUSION: Patients with nAMD required fewer injections after endophthalmitis, suggesting a biological change in disease activity. Neovascular age-related macular degeneration became quiescent in 13.3% of eyes. Most achieved better outcomes with anti-VEGF reinitiation.

PERIPAPILLARY PACHYCHOROID SYNDROME.

PURPOSE: To describe the features of peripapillary pachychoroid syndrome (PPS), a novel pachychoroid disease spectrum (PDS) entity. METHODS: Medical records of 31 eyes (16 patients) with choroidal thickening associated with intraretinal and/or subretinal fluid in the nasal macula extending from the disk were reviewed (patients with PPS). Choroidal thickness was compared with 2 age-matched cohorts: typical PDS (17 eyes with central serous chorioretinopathy or pachychoroid neovasculopathy) and 19 normal eyes. RESULTS: The patients with PPS were 81% men aged 71 ± 7 years. Peripapillary pachychoroid syndrome eyes displayed thicker nasal versus temporal macular choroids, unlike PDS eyes with thicker temporal macular choroids (P < 0.0001). Peripapillary intraretinal and/or subretinal fluid was often overlying dilated Haller layer vessels (pachyvessels). Fundus autofluorescence and fluorescein angiography illustrated peripapillary pigmentary mottling without focal leakage. Most PPS eyes (70%) exhibited other PDS findings including serous pigment epithelial detachment or gravitational tracks. Indocyanine green angiography illustrated dilated peripapillary pachyvessels and choroidal hyperpermeability. The disk was usually crowded, with edema noted in 4/31 (13%) eyes and mild late fluorescein disk leakage identified in half of the cases. Choroidal folds (77%), short axial lengths (39% less than 23 mm), and hyperopia (86%) were common. CONCLUSION: Peripapillary pachychoroid syndrome is a distinct PDS variant, in which peripapillary choroidal thickening is associated with nasal macular intraretinal and/or subretinal fluid and occasional disk edema. Recognition of PPS is important to distinguish it from disorders with overlapping features such as posterior uveitis and neuro-ophthalmologic conditions.

Percutaneous Patent Foramen Ovale Closure: Stroke and Beyond.

Over 750,000 individuals suffer from stroke annually in the United States, with 87% of these strokes being ischemic in nature. Roughly 40% of ischemic strokes occur in individuals 60 years of age or under. A quarter of all ischemic strokes have no identifiable cause despite extensive workup and are deemed cryptogenic in nature. Patent Foramen Ovales (PFO) has been postulated in stroke causation by either paradoxical embolization or platelet activation in the tunnel of the defect. The incidence of PFO is reported to be 15-25% in the general population but rises to 40% in patients with cryptogenic stroke. While the initial trials evaluating PFO closures were non-revealing, subsequent long-term follow-ups, as well as recent trials evaluating PFO closures in cryptogenic stroke patients 60 years of age or under, demonstrated the superiority of percutaneous closure compared to medical therapy alone, leading to FDA approval of PFO closure devices. In this review, we review the diagnosis of PFO, postulated stroke mechanisms, literature supporting PFO closure, patient selection for percutaneous closure, procedural considerations, and associated procedural complications.

Posterior Retinal Breaks Secondary to Closed-Globe Blunt Ocular Trauma.

Purpose: To describe 2 cases of posterior pole retinal tears resulting from closed-globe trauma. Methods: Two cases of retinal breaks in the posterior pole after blunt ocular trauma were evaluated, and the relevant literature was reviewed. Results: Two eyes of 2 patients with posterior pole retinal tears secondary to closed-globe trauma were included. One patient had a pars plana vitrectomy with laser retinopexy and gas tamponade; the final Snellen visual acuity (VA) was 20/200. The second patient was treated with indirect laser retinopexy; the final Snellen VA was counting fingers. Conclusions: The rapid deformation of the globe in response to blunt ocular trauma may create significant tangential stress on the retina, leading to stretch breaks in the posterior pole. Clinicians should follow patients with a closed-globe injury to watch for retinal breaks in the posterior pole, in particular when a hemorrhage or other pathology obscures the view.

Multifocal Vitelliform Paravascular Retinopathy (MVPR): A New Disorder in the Vitelliform Spectrum.

PURPOSE: To describe a new retinal phenotype characterized by bilateral, multifocal, subretinal vitelliform lesions along the vascular arcades that we refer to as multifocal vitelliform paravascular retinopathy (MVPR). DESIGN: Observational case series. METHODS: Multimodal retinal imaging including color fundus photography, fundus autofluorescence and cross sectional and en-face optical coherence tomography was performed to evaluate and characterize the lesions of MVPR. RESULTS: Thirteen asymptomatic patients aged 10 to 78 [mean 49±24, 49% under 50] were evaluated for bilateral retinal lesions. Initial visual acuity was 20/30 or better in 22 (85%) eyes. Of the 20 eyes with follow-up, 14 (70%) exhibited visual acuity 20/30 or better at final follow-up. Multifocal small round yellow lesions with distinct borders were identified along the vascular arcades in all patients. The vitelliform lesions were brightly hyperautofluorescent and consisted of focal areas of subretinal hyperreflective material on optical coherence tomography (OCT) that in some cases evolved to hyporeflective spaces (or retinal pigment epithelium atrophy) with associated hypoautofluorescence. When performed, electroretinography (ERG) and electrooculography (EOG) testing were normal and genetic testing was negative for variants in BEST1 and other genes associated with vitelliform retinopathies. CONCLUSIONS: MVPR may represent a novel entity of vitelliform disorders with a distinct clinical presentation and phenotype and generally favorable prognosis.

Genetic analysis and multimodal imaging identify novel mtDNA 12148T>C leading to multisystem dysfunction with tissue-specific heteroplasmy.

Patients with mitochondrial disorders present with clinically diverse symptoms, largely driven by heterogeneous mutations in mitochondrial-encoded and nuclear-encoded mitochondrial genes. These mutations ultimately lead to complex biochemical disorders with a myriad of clinical manifestations, often accumulating during childhood on into adulthood, contributing to life-altering and sometimes fatal events. It is therefore important to diagnose and characterize the associated disorders for each mitochondrial mutation as early as possible since medical management might be able to improve the quality and longevity of life in mitochondrial disease patients. Here we identify a novel mitochondrial variant in a mitochondrial transfer RNA for histidine (mt-tRNA-his) [m.12148T>C], that is associated with the development of ocular, aural, neurological, renal, and muscular dysfunctions. We provide a detailed account of a family harboring this mutation, as well as the molecular underpinnings contributing to cellular and mitochondrial dysfunction. In conclusion, this investigation provides clinical, biochemical, and morphological evidence of the pathogenicity of m.12148T>C. We highlight the importance of multiple tissue testing and in vitro disease modeling in diagnosing mitochondrial disease.

Association between Subclinical Hypothyroidism and Incident Hypertension in Women: A Systematic Review and Meta-Analysis.

Subclinical hypothyroidism (SCH) has been found to be associated with an increased risk of cardiovascular diseases. However, there is no clear consensus on the relationship between SCH and hypertension (HTN). We sought to investigate the association between SCH and incident HTN in women. MEDLINE and EMBASE databases were searched for studies that reported the incidence of HTN in females with SCH versus without SCH. Pooled odds ratio (OR) and 95% confidence interval (CI) of the outcome were obtained using a random-effects model. Studies were also divided into the middle-aged (mean age < 65) and the older (mean age ≥ 65) subgroups, and a subgroup analysis was performed to examine the potential age-effect on the association between SCH and HTN. Nine studies with a total of 21,972 subjects met the inclusion criteria. SCH was found to be positively associated with HTN (OR = 1.32, 95% CI = 1.02-1.71). Such association varied depending on the age of women. In the middle-aged subgroup, SCH was more positively associated with HTN (OR = 1.64, 95% CI = 1.18-2.27), while there was no significant association in the older subgroup (OR = 0.97, 95% CI = 0.80-1.16). Our study showed that the middle-aged females with SCH had an increased risk of HTN, while there was no significant association in the older females with SCH.

Long QT-Syndrome With Torsades de Pointes Managed Considering Financial Constraints Faced by the Patient.

Long QT syndrome (LQTS) is a rare arrhythmogenic condition characterized by abnormally long QT intervals on an electrocardiogram. The prevalence varies between 1 in 3000 and 1 in 10,000 but often remains undiagnosed. It is responsible for 3000 to 4000 sudden deaths among children and adults in the United States alone. LQTS can lead to torsades de pointes which is seen as twisting of QRS complex on electrocardiogram. We report a case of a 35-year-old patient with LQTS who presented with syncope and was found to have torsades de pointes. After acute management the patient was advised for automatic implantable cardioverter defibrillator (AICD) but because of financial constraints, she was placed on beta-blockers and permanent pacemaker.

CRB1 related retinal degeneration with novel mutation.

PURPOSE: To describe novel and previously unreported genetic mutations in the CRB1 gene in a patient with retinal dystrophy. To increase the genotype-phenotype understanding of CRB1-related retinal degenerative diseases and describe patients' response to therapy. OBSERVATIONS: Patient was evaluated for progressive loss of central and peripheral vision. Fundus photography, fundus autofluorescence (FAF), fluorescein angiography (FA), and ocular-coherence tomography (OCT) were used in the evaluation. Genetic screening was performed to explore underlying mutations. Genetics revealed a previously reported, pathogenic variant in the CRB1 gene (c.2842+5G > A), and a novel mutation (c.4014T > A) whose clinical significance is uncertain due to the absence of conclusive evidence. This case is phenotypically unique in that CME was refractory to therapy, while CME in CRB1 related maculopathy typically responds well to treatment. CONCLUSIONS AND IMPORTANCE: This study adds a breadth of phenotypic understanding to genetic analysis in CRB1 related retinal degenerative conditions. The newly described CRB1 variant mutation c.4014T > A may portend a poor prognosis for CME responsiveness to therapy. Genetic testing in an otherwise unexplained CME event may be useful to identify underlying CRB1 variants and reveal genotype-phenotype correlations, which may alter the treatment plan and prognosis.