PURPOSE: To investigate the telescope use and driving patterns of bioptic drivers with age-related macular degeneration (AMD). METHODS: A questionnaire addressing telescope use and driving patterns was administered by telephone interview to three groups of bioptic drivers: AMD (n = 31; median 76 years); non-AMD first licensed with a bioptic (n = 38; 53 years); and non-AMD first licensed without a bioptic (n = 47; 37 years). Driving patterns of bioptic AMD drivers were also compared with those of normal vision (NV) drivers (n = 36; 74 years) and nonbioptic AMD drivers (n = 34; 79 years). RESULTS: Bioptic usage patterns of AMD drivers did not differ from those of the younger bioptic drivers and greater visual difficulty without the bioptic was strongly correlated with greater bioptic helpfulness. Bioptic AMD drivers were more likely to report avoidance of night driving than the age-similar NV drivers (P = 0.06). However, they reported less difficulty than the nonbioptic AMD drivers in all driving situations (P ≤ 0.02). Weekly mileages of bioptic AMD drivers were lower than those of the younger bioptic drivers (P < 0.001), but not the NV group (P = 0.54), and were higher than those of the nonbioptic AMD group (P < 0.001). CONCLUSIONS: Our results suggest that bioptic telescopes met the visual demands of drivers with AMD and that those drivers had relatively unrestricted driving habits. TRANSLATIONAL RELEVANCE: Licensure with a bioptic telescope may prolong driving of older adults with AMD; however, objective measures of bioptic use, driving performance, and safety are needed.
Driving is an important rehabilitation goal for patients with homonymous field defects (HFDs); however, whether or not people with HFDs should be permitted to drive is not clear. Over the last 15 years, there has been a marked increase in the number of studies evaluating the effects of HFDs on driving performance. This review of the literature provides a much-needed summary for practitioners and researchers, addressing the following topics: regulations pertaining to driving with HFDs, self-reported driving difficulties, pass rates in on-road tests, the effects of HFDs on lane position and steering stability, the effects of HFDs on scanning and detection of potential hazards, screening for potential fitness to drive, evaluating practical fitness to drive and the efficacy of interventions to improve driving of persons with HFDs. Although there is clear evidence from on-road studies that some people with HFDs may be rated as safe to drive, others are reported to have significant deficits in skills important for safe driving, including taking a lane position too close to one side of the travel lane, unstable steering and inadequate viewing (scanning) behaviour. Driving simulator studies have provided strong evidence of a wide range in compensatory scanning abilities and detection performance, despite similar amounts of visual field loss. Conventional measurements of visual field extent (in which eye movements are not permitted) do not measure such compensatory abilities and are not predictive of on-road driving performance. Thus, there is a need to develop better tests to screen people with HFDs for visual fitness to drive. We are not yet at a point where we can predict which HFD patient is likely to be a safe driver. Therefore, it seems only fair to provide an opportunity for individualised assessments of practical fitness to drive either on the road and/or in a driving simulator.
The purpose of this research was to determine the potential use of water-soluble anionic and cationic carbosilane dendrimers (generations 1-3) as mucoadhesive polymers in eyedrop formulations. Cationic carbosilane dendrimers decorated with ammonium -NH3(+) groups were prepared by hydrosylilation of Boc-protected allylamine and followed by deprotection with HCl. Anionic carbosilane dendrimers with terminal carboxylate groups were also employed in this study. In vitro and in vivo tolerance studies were performed in human ocular epithelial cell lines and rabbit eyes respectively. The interaction of dendrimers with transmembrane ocular mucins was evaluated with a surface biosensor. As proof of concept, the hypotensive effect of a carbosilane dendrimer eyedrop formulation containing acetazolamide (ACZ), a poorly water-soluble drug with limited ocular penetration, was tested after instillation in normotensive rabbits. The methodology used to synthesize cationic dendrimers avoids the difficulty of obtaining neutral -NH2 dendrimers that require harsher reaction conditions and also present high aggregation tendency. Tolerance studies demonstrated that both prototypes of water-soluble anionic and cationic carbosilane dendrimers were well tolerated in a range of concentrations between 5 and 10 μM. Permanent interactions between cationic carbosilane dendrimers and ocular mucins were observed using biosensor assays, predominantly for the generation-three (G3) dendrimer. An eyedrop formulation containing G3 cationic carbosilane dendrimers (5 μM) and ACZ (0.07%) (289.4 mOsm; 5.6 pH; 41.7 mN/m) induced a rapid (onset time 1 h) and extended (up to 7 h) hypotensive effect, and led to a significant increment in the efficacy determined by AUC0(8h) and maximal intraocular pressure reduction. This work takes advantage of the high-affinity interaction between cationic carbosilane dendrimers and ocular transmembrane mucins, as well as the tensioactive behavior observed for these polymers. Our results indicate that low amounts of cationic carbosilane dendrimers are well tolerated and able to improve the hypotensive effect of an acetazolamide solution. Our results suggest that carbosilane dendrimers can be used in a safe range of concentrations to enhance the bioavailability of drugs topically administered in the eye.
A 29-year-old woman with a history of 2 bone marrow transplants for acute myelogenous leukemia developed bilateral sequential dacryocystitis in the context of known ocular graft-versus-host disease. With each infection, the patient underwent uneventful dacryocystorhinostomy. Postoperatively, she developed severe dry eye disease requiring replacement of punctal plugs and use of a prosthetic replacement of the ocular surface ecosystem lens. Histopathologic and immunohistochemical examination of the lacrimal sac showed a dense diffuse nonfollicular lymphocytic subepithelial infiltrate in the lacrimal sac that contained moderately more T-cells than B-cells. This is the first report of acute dacryocystitis associated with graft-versus-host disease. The authors caution that similar patients may develop worsening of ocular surface dryness due to restoration of normal lacrimal outflow.
PURPOSE: To describe the outcomes of the use of rituximab in the treatment of refractory noninfectious scleritis. DESIGN: Retrospective case series. METHODS: Review of the medical charts of patients with noninfectious scleritis refractory to conventional immunomodulatory therapy who were seen at the Massachusetts Eye Research and Surgery Institution between 2005 and 2015. The primary outcome measure in this study was steroid-free remission. Secondary outcomes were favorable response (decrease in scleritis activity score) and decrease in steroid dependence. RESULTS: There were 15 patients, with a mean follow-up duration of 34 months. Fourteen patients (93.3%) showed a clinical improvement, with 13 (86.6%) achieving a scleritis activity score of zero at 6 months. To date, 2 patients continue to enjoy durable drug-free remission (28 and 32 months follow-up). There was only 1 adverse effect recorded (infusion hypotension) requiring cessation of rituximab. CONCLUSION: Rituximab can be an effective treatment modality for recalcitrant noninfectious scleritis and, in some, can result in long-term durable drug-free remission.
Colour vision is only achieved in the presence of healthy and functional cone photoreceptors found in the retina. It is an essential component of human vision and usually the first complaint patients undergoing vision degeneration have is the loss of daylight colour vision. Therefore, an understanding of the biology and basic mechanisms behind cone death under the degenerative state of retinal dystrophies and how the activation of the apoptotic pathway is triggered will provide valuable knowledge. It will also have broader applications for a spectrum of visual disorders and will be critical for future advances in translational research.
More than one hundred naturally occurring variants of adeno-associated virus (AAV) have been identified, and this library has been further expanded by an array of techniques for modification of the viral capsid. AAV capsid variants possess unique antigenic profiles and demonstrate distinct cellular tropisms driven by differences in receptor binding. AAV capsids can be chemically modified to alter tropism, can be produced as hybrid vectors that combine the properties of multiple serotypes, and can carry peptide insertions that introduce novel receptor-binding activity. Furthermore, directed evolution of shuffled genome libraries can identify engineered variants with unique properties, and rational modification of the viral capsid can alter tropism, reduce blockage by neutralizing antibodies, or enhance transduction efficiency. This large number of AAV variants and engineered capsids provides a varied toolkit for gene delivery to the CNS and retina, with specialized vectors available for many applications, but selecting a capsid variant from the array of available vectors can be difficult. This chapter describes the unique properties of a range of AAV variants and engineered capsids, and provides a guide for selecting the appropriate vector for specific applications in the CNS and retina.
OBJECTIVE: Nonarteritic anterior ischemic optic neuropathy (NAION) is a devastating ocular condition causing permanent vision loss. Little is known about risk factors for developing this disease. We assessed demographic, systemic, and ocular factors associated with NAION. DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: Beneficiaries between 40 and 75 years old without NAION at baseline enrolled in a large U.S. managed care network. METHODS: Enrollees were monitored continuously for ≥2 years between 2001 and 2014 to identify those newly diagnosed with NAION (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] code 377.41). All persons were under ophthalmic surveillance and all cases had ≥1 confirmatory ICD-9-CM code for NAION during follow-up. MAIN OUTCOME MEASURES: Multivariable Cox regression modeling was used to generate hazard ratios (HRs) with 95% confidence intervals (CIs) to describe the statistical relationship between selected demographic characteristics, systemic and ocular conditions, and the hazard of developing NAION. RESULTS: Of 1 381 477 eligible enrollees, 977 (0.1%) developed NAION during a mean ± standard deviation (SD) follow-up of 7.8±3.1 years. The mean ± SD age for NAION cases at the index date was 64.0±9.2 years vs. 58.4±9.4 years for the remainder of the beneficiaries. After adjustment for confounding factors, each additional year older was associated with a 2% increased hazard of NAION (HR = 1.02; 95% CI: 1.01-1.03). Female subjects had a 36% decreased hazard of developing NAION (HR = 0.64; 95% CI: 0.55-0.74) compared with male subjects. Compared with whites, Latinos had a 46% decreased hazard of developing NAION (HR = 0.54; 95% CI: 0.36-0.82), whereas African ancestry was not significantly associated with NAION (HR = 0.91; 95% CI: 0.72-1.15). Systemic diseases associated with NAION included hypertension (HR = 1.62; 95% CI: 1.26-2.07) and hypercoagulable states (HR = 2.46; 95% CI: 1.51-4.00). Although diabetes mellitus (DM) was not significantly associated with NAION compared with those without DM (P = 0.45), patients with end-organ involvement from DM had a 27% increased hazard of NAION relative to those with uncomplicated DM (HR = 1.27; 95% CI: 1.01-1.59). Ocular diseases associated with NAION were age-related macular degeneration (HR = 1.29; 95% CI: 1.08-1.54) and retinal vein occlusion (HR = 3.94; 95% CI: 3.11-4.99). CONCLUSIONS: Our study identified several modifiable risk factors that may be associated with NAION. Should future studies confirm these findings, they may offer opportunities to prevent or treat this debilitating condition.
IMPORTANCE: Understanding the criteria for when strabismus becomes detectable by non-health care professionals could influence the goals for determining the success of surgical intervention and how patients with such misalignments are counseled. OBJECTIVE: To examine the magnitude at which strabismus is detectable by lay observers in an ethnically diverse set of images. DESIGN, SETTING, AND PARTICIPANTS: Photographs of 12 ethnically diverse models (black, white, and Asian) were simulated to have strabismus from esotropia of 21 prism diopters (∆) to exotropia of 21∆. From July 1, 2007, to October, 1, 2008, images were presented to 120 non-health care professionals aged 21 years or older from the general community in Boston, Massachusetts, who were asked whether strabismus was present. Analysis was conducted from November 1, 2008, to March 31, 2009. MAIN OUTCOMES AND MEASURES: The threshold angle for detecting strabismus to enable 70% of lay observers to make a positive determination whether strabismus is present. RESULTS: In white and black models, the threshold allowing a 70% positive detection rate was higher for esotropia than for exotropia (P < .001 for both). For white models, the threshold was 23.2∆ (95% CI, 21.0∆ to 26.5∆) for esotropia and 13.5∆ (95% CI, 12.5∆ to 14.6∆) for exotropia. For black models, the threshold was 20.8∆ (95% CI, 19.2∆ to 22.2∆) for esotropia and 16.3∆ (95% CI, 15.5∆ to 17.2∆) for exotropia. Asian models showed an opposite trend, with the threshold allowing a 70% positive detection rate for esotropia (14.3∆; 95% CI, 13.2∆ to 15.7∆) being lower than that for exotropia (20.9∆; 95% CI, 18.0∆ to 24.6∆) (P < .001). CONCLUSIONS AND RELEVANCE: Esotropia was easier for lay observers to detect than exotropia in Asian models, and exotropia was easier to detect than esotropia in white and black models. This information should be considered when managing patients who have concerns about the social significance of their strabismus. Future studies should include diverse individuals and make an effort to account for individual factors that may alter the perception of strabismus.
In March 2015, a meeting was held in London, United Kingdom, to address the progress in targeting the unmet need for dry eye disease (DED) treatment. The meeting, which launched the i(2) = initiating innovation series, was sponsored by the Tear Film & Ocular Surface Society (TFOS; www.TearFilm.org) and supported by Dompé. The TFOS i(2) meeting was designed to review advances in the understanding of DED since publication of the 2007 TFOS International Dry Eye WorkShop (DEWS) report, and to help launch the highly anticipated sequel, DEWS II. The meeting was structured to discuss the scope of the DED problem, to review the clinical challenges of DED, and to consider the treatment challenges of DED. This article provides a synopsis of the presentations of this TFOS i(2) meeting.
Shorter axial length observed in patients with primary angle closure glaucoma (PACG) might be due to altered matrix metalloproteinase-9 (MMP9) activity resulting in ECM remodeling during eye growth and development. This study aimed to evaluate common variants in MMP9 for association with PACG. Six tag SNPs of MMP9 were genotyped in a Chinese sample of 1,030 cases, including 572 PACG and 458 primary angle closure (PAC), and 499 controls. None of 6 SNPs were significantly associated with overall PAC/PACG (P > 0.07) or with PAC/PACG subgroups (Pc > 0.18). Meta-analysis of two non-Chinese studies revealed significant association between rs17576 and PACG (ORs = 0.56, P < 0.0001); however, meta-analysis of our dataset with 4 Chinese datasets did not replicate this association (ORs = 1.23, P = 0.29). Prior significant association for rs3918249 in one Caucasian study (OR = 0.63, P = 0.006) was not replicated in meta-analysis of 3 Chinese studies including this study (ORs = 0.91, P = 0.13). Significant heterogeneity between non-Chinese and Chinese datasets precluded overall meta-analysis for rs17576 and rs3918249 (Q = 0.001 and 0.04 respectively). rs17577 was nominally associated with PACG in one Caucasian study (OR = 1.71, P = 0.02), but not in 3 Chinese studies including our study (ORs = 1.20, P = 0.07). Overall meta-analysis revealed nominal association for rs17577 and PAC/PACG (ORs = 1.26, Pc = 0.05). Meta-analysis did not show significant association between the other SNPs and PAC/PACG (P > 0.47). The largest association study to date did not find significant association between MMP9 and PAC/PACG in Chinese; meta-analysis with other Chinese datasets did not produce significant association. In most instances combination with non-Chinese datasets was not possible except for one variant showing nominally significant association. More work is needed to define the role of MMP9 variants in PACG.
BACKGROUND: Acute respiratory infections (ARI) are the major worldwide health problem associated with high morbidity and mortality rates. Human adenovirus (HAdV) is one of the most common pathogens associated with viral ARI, and thus calls for specific diagnosis and better understanding of the epidemiology and clinical characteristics. METHODS: Total 4,130 children with ARI requiring hospitalization from 2012 to 2013 were retrospectively studied. Throat swab specimens were collected from each patient. Fluorescence Quantitative PCR was performed to detect adenovirus as well as other common ARI-related pathogens. The seven HAdV hypervariable regions (HVRs) of the hexon gene from fifty-seven HAdVs-positive samples collected in the seasonal peaks were sequenced. Phylogenetic analysis of HVRs was also conducted to confirm the molecular types and genetic variation. In addition, epidemiological features and co-infection with other human respiratory pathogens were investigated and analyzed. RESULTS: Of 4,130 hospitalized pediatric patients tested, the positive rates of respiratory syncytial virus (RSV), Mycoplasma pneumoniae (MP), and HAdV were 13.7%, 13.2%, and 12.0%, respectively. The HAdV positive patients accounted for 7.9%, 17.2%, 17.5% and 10.7% in age groups <1, 1-3, 3-6 and 6-14 years, respectively. Eighty-four HAdV positive children were co-infected with other respiratory pathogens (84/495, 17.0%). The most common co-infection pathogens with HAdV were MP (57.1%) and Human Bocavirus (HBoV) (16.7%). The majority of HAdV infected patients were totally recovered (96.9%, 480/495); However, four (0.8%) patients, who were previously healthy and at the age of 2 years or younger died of pneumonia. Seasonal peaks of HAdV infection occurred in the summer season of 2012 and 2013; the predominant HAdV type was HAdV-3 (70%), followed by HAdV-7 (28%). These epidemiological features were different from those in Northern China. The HAdV-55 was identified and reported for the first time in Guangzhou metropolitan area. Phylogenetic analysis indicated that all the HVR sequences of the hexon gene of HAdV-3 and -7 strains have high similarity within their individual types, and these strains were also similar to those circulating in China currently, indicating the conservation of hexon genes of both HAdV-3 and HAdV-7. CONCLUSIONS: Knowledge of the epidemiological features and molecular types of HAdV, a major pathogen of pediatric ARI, as well as other co-infected respiratory pathogens circulating in Guangzhou, southern China, is vital to predict and prevent future disease outbreaks in children. This study will certainly facilitate HAdV vaccine development and treatment of HAdV infections in children.
PURPOSE: To report 2 immunocompromised patients with sino-orbital necrotizing pseudomonas infections and review the literature. METHODS: This is a noncomparative, retrospective case series, and review. The clinical data of 2 patients with histopathologic and microbiologic diagnoses of pseudomonas sinus infections causing orbital cellulitis were obtained from medical records. A retrospective literature review was performed on all reported cases of periorbital pseudomonas infections. RESULTS: One patient with acquired immune deficiency syndrome was noted to have orbital cellulitis with clear visualization of eschar in the middle turbinate on nasal endoscopy. A second patient also had orbital cellulitis with ophthalmoplegia and presence of eschar in the sinus. Both patients had some degree of erosion through the lamina papyracea found on orbital imaging and both had intact vision without optic neuropathy. Pseudomonas infection was confirmed in both cases with permanent histopathology and cultures from conservative sinus debridement. CONCLUSIONS: Pseudomonas sino-orbital infections must be considered in the differential diagnosis in cases of eschar and orbital wall erosion especially when vision is preserved in immunocompromised individuals. This finding obviates the need for radical debridement including orbital exenteration, which can be indicated in cases of invasive fungal disease.
PURPOSE: To study the clinical features of endogenous endophthalmitis (EE) in sample patient populations from the USA and South Korea over an 8-year period. METHODS: We reviewed data from 128 eyes of 60 American and 48 Korean patients diagnosed with EE and compared their clinical characteristics. RESULTS: Fungemia and liver abscess were the most common extraocular infection sources among American (26.7%) and Korean patients (33.3%), respectively. Klebsiella pneumoniae and Candida species were the most common pathogens of EE in the Korean and the American patients, respectively. Endophthalmitis caused by fungi had a better visual prognosis than that caused by bacteria (p = 0.001). Vitrectomy was beneficial for eyes with EE due to virulent bacteria presenting with worse than counting finger vision. CONCLUSIONS: The predisposing conditions and responsible organisms for EE vary in different regions of the world. The visual prognosis was strongly influenced by the underlying pathogen.
PURPOSE: To describe the clinical course of uveitis-associated inflammatory papillitis and evaluate the utility and reproducibility of optic nerve spectral domain optical coherence tomography (SD-OCT). METHODS: Data on 22 eyes of 14 patients with uveitis-related papillitis and optic nerve imaging were reviewed. SD-OCT measure reproducibility was determined and parameters were compared in active vs. inactive uveitis. RESULTS: Papillitis resolution lagged behind uveitis resolution in three patients. For SD-OCT measures, the intraclass correlation coefficients were 99.1-100% and 86.9-100% for intraobserver and interobserver reproducibility, respectively. All SD-OCT optic nerve measures except inferior and nasal peripapillary retinal thicknesses were significantly higher in active vs. inactive uveitis after correction for multiple hypotheses testing. Mean optic nerve central thickness decreased from 545.1 to 362.9 µm (p = 0.01). CONCLUSIONS: Resolution of inflammatory papillitis can lag behind resolution of uveitis. SD-OCT assessment of papillitis is reproducible and correlates with presence vs. resolution of uveitis.
The aim of this article is to validate the accuracy of Facial Assessment by Computer Evaluation (FACE) program in eyelid measurements. Sixteen subjects between the ages of 27 and 65 were included with IRB approval. Clinical measurements of upper eyelid margin reflex distance (MRD1) and inter-palpebral fissure (IPF) were obtained. Photographs were then taken with a digital single lens reflex camera with built-in pop-up flash (dSLR-pop) and a dSLR with lens-mounted ring flash (dSLR-ring) with the cameras upright, rotated 90, 180, and 270 degrees. The images were analyzed using both the FACE and ImageJ software to measure MRD1 and IPF.Thirty-two eyes of sixteen subjects were included. Comparison of clinical measurement of MRD1 and IPF with FACE measurements of photos in upright position showed no statistically significant differences for dSLR-pop (MRD1: p = 0.0912, IPF: p = 0.334) and for dSLR-ring (MRD1: p = 0.105, IPF: p = 0.538). One-to-one comparison of MRD1 and IPF measurements in four positions obtained with FACE versus ImageJ for dSLR-pop showed moderate to substantial agreement for MRD1 (intraclass correlation coefficient = 0.534 upright, 0.731 in 90 degree rotation, 0.627 in 180 degree rotation, 0.477 in 270 degree rotation) and substantial to excellent agreement in IPF (ICC = 0.740, 0.859, 0.849, 0.805). In photos taken with dSLR-ring, there was excellent agreement of all MRD1 (ICC = 0.916, 0.932, 0.845, 0.812) and IPF (ICC = 0.937, 0.938, 0.917, 0.888) values. The FACE program is a valid method for measuring margin reflex distance and inter-palpebral fissure.