The mouse corneal micropocket assay is a robust and quantitative in vivo assay for evaluating angiogenesis. By using standardized slow-release pellets containing specific growth factors that trigger blood vessel growth throughout the naturally avascular cornea, angiogenesis can be measured and quantified. In this assay the angiogenic response is generated over the course of several days, depending on the type and dose of growth factor used. The induction of neovascularization is commonly triggered by either basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF). By combining these growth factors with sucralfate and hydron (poly-HEMA (poly(2-hydroxyethyl methacrylate))) and casting the mixture into pellets, they can be surgically implanted in the mouse eye. These uniform pellets slowly-release the growth factors over five or six days (bFGF or VEGF respectively) enabling sufficient angiogenic response required for vessel area quantification using a slit lamp. This assay can be used for different applications, including the evaluation of angiogenic modulator drugs or treatments as well as comparison between different genetic backgrounds affecting angiogenesis. A skilled investigator after practicing this assay can implant a pellet in less than 5 min per eye.
The ability to form biofilms in a variety of environments is a common trait of bacteria, and may represent one of the earliest defenses against predation. Biofilms are multicellular communities usually held together by a polymeric matrix, ranging from capsular material to cell lysate. In a structure that imposes diffusion limits, environmental microgradients arise to which individual bacteria adapt their physiologies, resulting in the gamut of physiological diversity. Additionally, the proximity of cells within the biofilm creates the opportunity for coordinated behaviors through cell-cell communication using diffusible signals, the most well documented being quorum sensing. Biofilms form on abiotic or biotic surfaces, and because of that are associated with a large proportion of human infections. Biofilm formation imposes a limitation on the uses and design of ocular devices, such as intraocular lenses, posterior contact lenses, scleral buckles, conjunctival plugs, lacrimal intubation devices and orbital implants. In the absence of abiotic materials, biofilms have been observed on the capsule, and in the corneal stroma. As the evidence for the involvement of microbial biofilms in many ocular infections has become compelling, developing new strategies to prevent their formation or to eradicate them at the site of infection, has become a priority.
BACKGROUND: Surgical management of intraconal pathology represents the next frontier in endoscopic endonasal surgery. Despite this, the medial intraconal space remains a relatively unexplored region, secondary to its variable and technically demanding anatomy. The purpose of this study is to define the neurovascular structures in this region and introduce a compartmentalized approach to enhance surgical planning. METHODS: This study was an institutional review board (IRB)-exempt endoscopic anatomic study in 10 cadaveric orbits. After dissection of the medial intraconal space, the pattern and trajectory of the oculomotor nerve and ophthalmic arterial arborizations were analyzed. The position of all vessels as well as the length of the oculomotor trunk and branches relative to the sphenoid face were calculated. RESULTS: A mean of 1.5 arterial branches were identified (n = 15; range, 1-4) at a mean of 8.8 mm from the sphenoid face (range, 4-15 mm). The majority of the arteries (n = 7) inserted adjacent to the midline of medial rectus. The oculomotor nerve inserted at the level of the sphenoid face and arborized with a large proximal trunk 5.5 ± 1.1 mm in length and multiple branches extending 13.2 ± 2.7 mm from the sphenoid face. The most anterior nerve and vascular pedicle were identified at 17.0 and 15.0 mm from the sphenoid face, respectively. CONCLUSION: The neurovascular supply to the medial rectus muscle describes a varied but predictable pattern. This data allows the compartmentalization of the medial intraconal space into 3 zones relative to the neurovascular supply. These zones inform the complexity of the dissection and provide a guideline for safe medial rectus retraction relative to the fixed landmark of the sphenoid face.
BACKGROUND: Endoscopic orbital surgery represents the next frontier in endonasal surgery. The current literature is largely composed of small, heterogeneous, case series with little consensus regarding optimal techniques. The purpose of this study was to combine the experience of multiple international centers to create a composite of the global experience on the endoscopic management of a single type of tumor, the orbital cavernous hemangioma (OCH). METHODS: This was a retrospective study of techniques for endoscopic OCH resection from 6 centers on 3 continents. Only primary data from strictly endoscopic resection of OCHs were included. Responses were analyzed to qualitatively identify points of both consensus and variability among the different groups. RESULTS: Data for a total of 23 patients, 10 (43.5%) male and 13 (56.5%) female were collected. The majority of lesions were intraconal (60.9%). The mean ± standard deviation (SD) surgical time was 150.7 ± 75.0 minutes with a mean blood loss of 82.7 ± 49.6 mL. Binarial approaches (26.1%) were used exclusively in the setting of intraconal lesions, which were associated with a higher rate of incomplete resection (31.3%), postoperative diplopia (25.0%), and the need for reconstruction (37.5%) than extraconal lesions. Orthotropia and symmetric orbital appearance were achieved in 60.9% and 78.3% of cases, respectively. CONCLUSION: Extraconal lesions were managed similarly; however, greater variability was evident for intraconal lesions. These included the laterality and number of hands in the approach, methods of medial rectus retraction, and the need for reconstruction. The increased technical complexity and disparity of techniques in addressing intraconal OCHs suggests that continued research into the optimal management of this subclass of lesions is of significant priority.
PURPOSE: To evaluate the effectiveness of a therapeutic trial of valganciclovir in patients with uveitis with positive Epstein-Barr virus early antigen D immunoglobulin G titers (EBV EA-D). METHODS: We performed a retrospective chart review of 14 patients at the Massachusetts Eye Research and Surgery Institution who had uveitis with positive EBV EA-D but negative studies for all other causes of uveitis and were treated with valganciclovir 450 mg twice a day or valganciclovir 900 mg twice a day between January 2010 and August 2014. RESULTS: Nine of 14 patients, who had presumed EBV reactivation with associated intraocular inflammation, were successfully treated with valganciclovir: 3 of these were treated with valganciclovir 450 mg twice a day and 6 were treated with valganciclovir 900 mg twice a day. Five of 14 patients failed to respond to valganciclovir with persistent inflammation after at least 2 weeks of valganciclovir therapy, and were subsequently treated with immunomodulatory therapy to control inflammation. CONCLUSIONS: Uveitis can be caused by EBV infection/reactivation. A therapeutic trial with valganciclovir 450 mg twice a day for 1 month in patients with uveitis with positive EBV EA antibody may be beneficial.
Importance: Common pathophysiological mechanisms may be responsible for immune dysregulation in both thyroid disease and uveitis. Studies investigating a possible association are limited. Objective: To determine the association between thyroid disease and uveitis. Design, Setting, and Participants: A retrospective, population-based case-control study was conducted from January 1, 2006, to December 31, 2007, among 217 061 members of the Kaiser Permanente Hawaii health system during the study period. A clinical diagnosis of uveitis was determined through a query of the electronic medical record followed by individual medical record review for confirmation by a uveitis specialist. Thyroid disease was determined based on International Classification of Diseases, Ninth Revision, coding. Two control groups were chosen at a 4:1 ratio for comparison with patients with uveitis. A logistic regression analysis was performed with uveitis as the main outcome variable and thyroid disease as the main predictor variable, while adjusting for age, sex, race, smoking status, and history of autoimmune disease. Data analysis was conducted between 2014 and 2016. Main Outcomes and Measures: A diagnosis of thyroid disease among patients with uveitis and respective controls. Results: Of the 224 patients with uveitis (127 women and 97 men; mean [SD] age, 54.1 [17.8] years) identified during the study period, 29 (12.9%) had a diagnosis of thyroid disease, compared with 62 of 896 patients (6.9%) in the control group (P = .01) and 78 of 896 patients (8.7%) in the ophthalmology clinic control group (P = .06). Using the general Kaiser Permanente Hawaii population control group, patients who had thyroid disease had a 1.7-fold (95% CI, 1.03-2.80; P = .04) higher odds of having uveitis compared with patients who did not have thyroid disease when controlling for age, sex, race, smoking status, and autoimmune disease. A similar association was found using the ophthalmology clinic control group (odds ratio, 1.8; 95% CI, 1.1-2.9; P = .02) while adjusting for these factors. Conclusions and Relevance: These findings suggest that a history of thyroid disease has a weak to moderate association with uveitis. Similar autoimmune mechanisms could explain the pathogenesis of both conditions. If future studies corroborate these findings, they may have further clinical implications in the laboratory workup of uveitis.
PURPOSE: To evaluate the effect of deliberate removal of the central Descemet membrane on endothelial function and morphology in patients with Fuchs endothelial dystrophy (FED) and cataract undergoing phacoemulsification. METHODS: In this retrospective case series, patients with FED and visually significant cataract underwent phacoemulsification in an academic cornea practice in Boston, MA. Four millimeters of the central Descemet membrane was stripped and removed after intraocular lens insertion. Vision, corneal pachymetry, and confocal imaging of the endothelial anatomy were performed before surgery and at 1, 3, 6, and 12 months after surgery. Patients were classified as fast responders, responders, slow responders, and nonresponders on the basis of postoperative time to resolution of corneal edema with visible central endothelial mosaic. RESULTS: Eleven patients (13 eyes) aged 51 to 91 years were included in the study. No eyes had countable central endothelial cells by confocal imaging before surgery. Preoperative visual acuity ranged from 20/25 to 20/400. All corneas showed stromal and microcystic edema in the area of Descemet stripping at days 1 and 7 after surgery. Four eyes demonstrated resolution of corneal edema with visible central endothelial cell mosaic (range: 410-864 cells/mm) by postoperative month 1 with visual acuity ranging between 20/25 and 20/40. Four additional eyes demonstrated a similar response by postoperative month 3 and an additional 2 eyes had resolution of corneal edema with an intact central endothelial mosaic at postoperative month 6 or later. Cell counts (range: 428-864 cells/mm) were maintained in all 10 responders at the last follow-up visit (range: postoperative months 6-24). Final vision ranged from 20/15 to 20/20 in these 10 eyes with the exception of 2 eyes with retinal pathology. Three eyes required endothelial keratoplasty. CONCLUSIONS: Repopulation of the central corneal endothelium with corneal deturgescence can occur after deliberate central Descemet stripping in patients with FED who underwent cataract removal. This may offer a novel treatment for patients with FED that could reduce the need for endothelial transplantation. Further studies are needed to delineate the optimal patient population for Descemet stripping because not all patients will respond to this intervention.
PURPOSE: To report strabismus surgery frequency and outcomes after monocular infantile cataract surgery with or without IOL implantation. METHODS: The Infant Aphakia Treatment Study (IATS) is a randomized, multicenter clinical trial comparing treatment of aphakia with a primary IOL or contact lens in 114 infants with a unilateral congenital cataract. This report is a secondary outcome analysis of ocular motor data from IATS patients who underwent strabismus surgery prior to age 5 years. RESULTS: Strabismus surgery was performed in 45 (39%) patients (contact lens group [CL], 37%; IOL group, 42% [P = 0.70]). The indications for strabismus surgery were esotropia (62%), exotropia (33%), and hypertropia (4%). Infants who underwent cataract surgery at a younger age were less likely to undergo strabismus surgery (28-48 days, 12/50 [24%]; 49-210 days, 33/64 [52%]; P = 0.0037). Of the 42 patients who underwent strabismus surgery, 14 (33%) had a postoperative distance alignment within 8(Δ) of orthotropia at age 5 years. The 5-year visual acuity of children with strabismus was the same whether or not strabismus surgery had been performed (1.10 logMAR with surgery vs 1.00 without [P = 0.71]). CONCLUSIONS: In this study cohort, cataract surgery performed in the first 6 weeks of life was associated with a reduced frequency of strabismus surgery. Strabismus surgery outcomes in this population are guarded. Surgical improvement of strabismus does not appear to influence long-term visual acuity.
BACKGROUND: Transient monocular vision loss (TMVL) is an alarming symptom owing to potentially serious etiologies such as thromboembolism or giant cell arteritis. Our objective is to describe the phenomenon of TMVL present on awakening, which may represent a distinct and benign entity. METHODS: We performed a retrospective observational case series of 29 patients who experienced TMVL on awakening. Patients who described monocular dimming or blackout of vision were included, and those with blurred vision, concurrent eye pain, and binocular vision loss were excluded. Descriptive statistics were used to summarize the study population. RESULTS: Of the 29 patients we studied, 90% (n = 26) were female and 48% had crowded discs (cup-to-disc ratio ≤0.2). The mean age was 45.4 years, although women were significantly younger than men (mean ages 43.4 and 62.7 years, respectively, P = 0.017). Brain magnetic resonance imaging and vascular imaging (magnetic resonance angiography, computed tomographic angiography, or carotid Doppler) were performed in 69% and 55% of cases, respectively, and were uniformly negative. In 14 patients for whom clear follow-up data could be obtained, no medically or visually significant sequelae of this syndrome were found, and 50% experienced resolution of symptoms. CONCLUSIONS: Evaluation was uniformly negative when patients described waking with isolated vision loss in 1 eye with subsequent resolution, usually in less than 15 minutes. The natural history seems benign with symptoms frequently remitting spontaneously. This visual phenomenon may represent an autoregulatory failure resulting in a supply/demand mismatch during low-light conditions.
There are no data in the literature regarding the safety of re-treatment with ethambutol for recurrent mycobacterial infection after prior ethambutol-induced optic neuropathy. We describe a patient who developed optic neuropathy attributed to ethambutol, recovered fully after drug withdrawal, and tolerated a 14-month long re-treatment 10 years later without developing recurrent optic neuropathy.
Diplopia after cataract extraction is an unexpected outcome for the patient and often a source of confusion for the physician, owing to its relative infrequency. This article reviews the pertinent literature on the subject. Mechanisms include anesthetic myotoxicity, surgical trauma, optical aberrations, cortical disorders in patients with congenital strabismus, and the unmasking of previously unnoticed ocular misalignment. As the population continues to age and cataract extraction is performed in increasing volume, familiarity with this uncommon but important outcome may help to clarify and effectively treat post-cataract-extraction diplopia.
OBJECTIVE: This case series is the first to describe divergence palsy as an adverse effect of antiepileptic drug use. Diplopia is a common adverse effect of antiepileptic drugs, but no explanatory motility deficit has ever been reported. METHODS: We present 2 patients, 1 on oxcarbazepine and 1 on divalproex, each with a normal examination result between spells and divergency palsy when symptomatic. RESULTS: Discontinuation of the antiepileptic medication led to resolution of the episodes in both cases. Rechallenge with the offending agent after washout in one patient resulted in recurrence of diplopia and divergence palsy, both resolving after subsequent withdrawal of the antiepileptic. CONCLUSIONS: Antiepileptic drugs may cause divergence palsy.
BACKGROUND: Global and regional prevalence estimates for blindness and vision impairment are important for the development of public health policies. We aimed to provide global estimates, trends, and projections of global blindness and vision impairment. METHODS: We did a systematic review and meta-analysis of population-based datasets relevant to global vision impairment and blindness that were published between 1980 and 2015. We fitted hierarchical models to estimate the prevalence (by age, country, and sex), in 2015, of mild visual impairment (presenting visual acuity worse than 6/12 to 6/18 inclusive), moderate to severe visual impairment (presenting visual acuity worse than 6/18 to 3/60 inclusive), blindness (presenting visual acuity worse than 3/60), and functional presbyopia (defined as presenting near vision worse than N6 or N8 at 40 cm when best-corrected distance visual acuity was better than 6/12). FINDINGS: Globally, of the 7·33 billion people alive in 2015, an estimated 36·0 million (80% uncertainty interval [UI] 12·9-65·4) were blind (crude prevalence 0·48%; 80% UI 0·17-0·87; 56% female), 216·6 million (80% UI 98·5-359·1) people had moderate to severe visual impairment (2·95%, 80% UI 1·34-4·89; 55% female), and 188·5 million (80% UI 64·5-350·2) had mild visual impairment (2·57%, 80% UI 0·88-4·77; 54% female). Functional presbyopia affected an estimated 1094·7 million (80% UI 581·1-1686·5) people aged 35 years and older, with 666·7 million (80% UI 364·9-997·6) being aged 50 years or older. The estimated number of blind people increased by 17·6%, from 30·6 million (80% UI 9·9-57·3) in 1990 to 36·0 million (80% UI 12·9-65·4) in 2015. This change was attributable to three factors, namely an increase because of population growth (38·4%), population ageing after accounting for population growth (34·6%), and reduction in age-specific prevalence (-36·7%). The number of people with moderate and severe visual impairment also increased, from 159·9 million (80% UI 68·3-270·0) in 1990 to 216·6 million (80% UI 98·5-359·1) in 2015. INTERPRETATION: There is an ongoing reduction in the age-standardised prevalence of blindness and visual impairment, yet the growth and ageing of the world's population is causing a substantial increase in number of people affected. These observations, plus a very large contribution from uncorrected presbyopia, highlight the need to scale up vision impairment alleviation efforts at all levels. FUNDING: Brien Holden Vision Institute.
BACKGROUND: Within a surveillance of the prevalence and causes of vision impairment in high-income regions and Central/Eastern Europe, we update figures through 2015 and forecast expected values in 2020. METHODS: Based on a systematic review of medical literature, prevalence of blindness, moderate and severe vision impairment (MSVI), mild vision impairment and presbyopia was estimated for 1990, 2010, 2015, and 2020. RESULTS: Age-standardised prevalence of blindness and MSVI for all ages decreased from 1990 to 2015 from 0.26% (0.10-0.46) to 0.15% (0.06-0.26) and from 1.74% (0.76-2.94) to 1.27% (0.55-2.17), respectively. In 2015, the number of individuals affected by blindness, MSVI and mild vision impairment ranged from 70 000, 630 000 and 610 000, respectively, in Australasia to 980 000, 7.46 million and 7.25 million, respectively, in North America and 1.16 million, 9.61 million and 9.47 million, respectively, in Western Europe. In 2015, cataract was the most common cause for blindness, followed by age-related macular degeneration (AMD), glaucoma, uncorrected refractive error, diabetic retinopathy and cornea-related disorders, with declining burden from cataract and AMD over time. Uncorrected refractive error was the leading cause of MSVI. CONCLUSIONS: While continuing to advance control of cataract and AMD as the leading causes of blindness remains a high priority, overcoming barriers to uptake of refractive error services would address approximately half of the MSVI burden. New data on burden of presbyopia identify this entity as an important public health problem in this population. Additional research on better treatments, better implementation with existing tools and ongoing surveillance of the problem is needed.
Interventions in the treatment of mild to moderate glaucoma have evolved to include a group of procedures collectively named "Minimally Invasive Glaucoma Surgery (MIGS)." These procedures are less invasive than traditional filtering surgery and setons and offer the benefit of an improved side-effect profile. A review of current published literature has shown that these procedures offer lower intraocular pressure, decrease reliance on topical medications, have no negative effect on refractive outcomes, and can be safely done following failed tube surgery.
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.
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.