Preliminary Safety and Efficacy of Head and Neck Cooling Therapy After Concussion in Adolescent Athletes: A Randomized Pilot Trial.

OBJECTIVE: To determine the safety and efficacy of head and neck cooling when applied up to 8 days after concussion among adolescent athletes. DESIGN: A randomized nonblinded pilot trial. SETTING: Sports Medicine Clinic in a tertiary hospital. PATIENTS: Adolescent athletes aged 12 to 17 years diagnosed with a concussion within 1 week of injury. INTERVENTIONS AND MAIN OUTCOME MEASURES: The control group (n = 27) received standard treatment (short term brain rest), whereas the treatment group (n = 28) received standard treatment and head and neck cooling. Head and neck cooling treatment was applied to patients at the postinjury assessment visit and at 72 hours post-injury. The SCAT5 (Sport Concussion Assessment Tool) total symptom severity score was collected at postinjury assessment visit, pre- and post-treatment at 72 hours, and at 10 days, and 4 weeks post-treatment. RESULTS: Athletes who received head and neck cooling had a faster symptom recovery ( P = 0.003) and experienced significant reduction in symptom severity scores after treatment ( P < 0.001). Sport type and gender did not influence the treatment outcome ( P = 0.447 and 0.940, respectively). CONCLUSIONS: This pilot study demonstrates feasibility of head and neck cooling for the management of acute concussion in adolescent athletes.

Shewanella oneidensis MR-1 nanowires are outer membrane and periplasmic extensions of the extracellular electron transport components.

Bacterial nanowires offer an extracellular electron transport (EET) pathway for linking the respiratory chain of bacteria to external surfaces, including oxidized metals in the environment and engineered electrodes in renewable energy devices. Despite the global, environmental, and technological consequences of this biotic-abiotic interaction, the composition, physiological relevance, and electron transport mechanisms of bacterial nanowires remain unclear. We report, to our knowledge, the first in vivo observations of the formation and respiratory impact of nanowires in the model metal-reducing microbe Shewanella oneidensis MR-1. Live fluorescence measurements, immunolabeling, and quantitative gene expression analysis point to S. oneidensis MR-1 nanowires as extensions of the outer membrane and periplasm that include the multiheme cytochromes responsible for EET, rather than pilin-based structures as previously thought. These membrane extensions are associated with outer membrane vesicles, structures ubiquitous in Gram-negative bacteria, and are consistent with bacterial nanowires that mediate long-range EET by the previously proposed multistep redox hopping mechanism. Redox-functionalized membrane and vesicular extensions may represent a general microbial strategy for electron transport and energy distribution.

Proteomic analysis of keratitis-associated Pseudomonas aeruginosa.

PURPOSE: To compare the proteomic profile of a clinical isolate of Pseudomonas aeruginosa (P. aeruginosa) obtained from an infected cornea of a contact lens wearer and the laboratory strain P. aeruginosa ATCC 10145. METHODS: Antibiotic sensitivity, motility, biofilm formation, and virulence tests were performed using standard methods. Whole protein lysates were analyzed with liquid chromatography/ tandem mass spectrometry (LC-MS/MS) in triplicate, and relative protein abundances were determined with spectral counting. The G test followed by a post hoc Holm-Sidak adjustment was used for the statistical analyses to determine significance in the differential expression of proteins between the two strains. RESULTS: A total of 687 proteins were detected. One-hundred thirty-three (133) proteins were significantly different between the two strains. Among these, 13 were upregulated, and 16 were downregulated in the clinical strain compared to ATCC 10145, whereas 57 were detected only in the clinical strain. The upregulated proteins are associated with virulence and pathogenicity. CONCLUSIONS: Proteins detected at higher levels in the clinical strain of P. aeruginosa were proteins known to be virulence factors. These results confirm that the keratitis-associated P. aeruginosa strain is pathogenic and expresses a higher number of virulence factors compared to the laboratory strain ATCC 10145. Identification of the protein profile of the corneal strain of P. aeruginosa in this study will aid in elucidating novel intervention strategies for reducing the burden of P. aeruginosa infection in keratitis.

MicroRNA in aqueous humor from patients with cataract.

MicroRNAs (miRNAs) are small non-coding RNA molecules with regulatory function and marked tissue specificity that can modulate multiple gene targets. They have been detected in body fluids and are associated with various physiologic and pathologic processes. We analyzed aqueous humor (AH) from human subjects undergoing cataract surgery to establish the presence and relative quantities of known miRNAs. AH was collected from patients without known ocular diseases other than cataract and a normal systemic history. Quantitative real-time PCR in an array platform was used to detect known miRNAs present in the AH. Among the 264 miRNAs tested, 110 were present in the AH. The top 5 abundant miRNAs identified were miR-202, miR-193b, miR-135a, miR-365, and miR-376a. The presence of miRNAs in AH suggests that they may have functional roles in regulating target genes in tissues lining the anterior chamber. Further analysis of the AH miRNA population may identify potential gene targets and provide insights regarding their roles in AH regulation, glaucoma and anterior segment disease processes.

Immunohistochemical expression and distribution of proteoglycans and collagens in sclerocornea.

To immunolocalize corneal keratan sulfate (KS) and its core protein lumican, aggrecan, type I and type III collagens in sclerocornea specimens and compare their expression and distribution to age-matched healthy corneas and scleras. Sclerocornea specimens (n = 3) and age-matched normal corneoscleral rim specimens (n = 3) were studied by light microscopy and histochemically. KS, lumican, aggrecan, type I and type III collagens were immunolocalized in the specimens using indirect immunofluorescence. The fluorescence intensity in each specimen was scored from 0 to 4, with 0 representing no fluorescence and 4 representing intense fluorescence. The sclerocornea specimens showed histologic features typical of sclerocornea. KS and lumican immunolabeling in the corneal stroma in sclerocornea was decreased, whereas aggrecan immunolabeling was increased compared to that seen in normal cornea and normal sclera. KS and lumican staining was more intense in the posterior part of sclerocornea specimens, whereas aggrecan staining was distributed throughout the stroma. The staining intensity and distribution of type I collagen in sclerocornea was similar to that seen in normal cornea. Type III collagen was faint to absent in both normal cornea and sclerocornea but strong labeling was noted in normal sclera. The immunophenotype of sclerocornea is similar to that of normal cornea but with reduced labeling intensity of KS and lumican and increased labeling intensity of aggrecan. This change could potentially contribute to the abnormal fibril assembly in sclerocornea.

Congenital ectropion uvea and mechanisms of glaucoma in neurofibromatosis type 1: new insights.

OBJECTIVE: To describe the clinicopathologic features of congenital ectropion uvea associated with glaucoma in neurofibromatosis-1 (NF-1). DESIGN: Retrospective case series. PARTICIPANTS AND CONTROLS: Five cases of NF-1 associated with glaucoma, from which enucleated eyes were available, and 2 eye bank eyes used as controls. METHODS: The clinical features and courses of these patients were reviewed. Formalin-fixed, paraffin-embedded eyes were examined by light and electron microscopy. Immunohistochemistry using antineurofibromin, anti-glial fibrillary acidic protein, and antivimentin was performed in 3 patients. Gene expression of the mitogen-activated protein kinase (MAPK) signaling pathway was examined in corneal endothelial cells in 1 patient. MAIN OUTCOME MEASURES: Cause of glaucoma in patients with ectropion uvea and NF-1. RESULTS: The age of patients at the time of glaucoma diagnosis ranged from birth to 13 years. Four of the 5 patients had megalocornea and buphthalmos at presentation. Ectropion uvea was noted clinically in 2 patients, but was demonstrated histopathologically in all 5 patients. On histopathologic examination, all patients had varying degrees of angle closure secondary to endothelialization of the anterior chamber angle. Uveal neurofibromas were noted in all patients; anteriorly displaced ciliary processes were noted in 4 of 5 patients who demonstrated ciliary body involvement with neurofibromas. Absence of Schlemm's canal was observed. The endothelial cells lining the closed angle demonstrated positive stain results with the vimentin antibody. Positive antineurofibromin immunolabeling was detected in normal control corneal endothelium, but was absent in corneal endothelium in patients with endothelialization of the angle. Upregulation of genes from the MAPK signaling pathway was demonstrated in the corneal endothelial cells isolated from the NF-1 eyes. CONCLUSIONS: Ectropion uvea in NF-1 glaucoma is secondary to endothelialization of the anterior chamber angle and is associated commonly with severe pediatric glaucoma in NF-1 patients. The endothelial cell proliferation may be related to overexpression of the Ras (Rat sarcoma)-MAPK genes in these eyes.

Animal models of glaucoma.

Glaucoma is a heterogeneous group of disorders that progressively lead to blindness due to loss of retinal ganglion cells and damage to the optic nerve. It is a leading cause of blindness and visual impairment worldwide. Although research in the field of glaucoma is substantial, the pathophysiologic mechanisms causing the disease are not completely understood. A wide variety of animal models have been used to study glaucoma. These include monkeys, dogs, cats, rodents, and several other species. Although these models have provided valuable information about the disease, there is still no ideal model for studying glaucoma due to its complexity. In this paper we present a summary of most of the animal models that have been developed and used for the study of the different types of glaucoma, the strengths and limitations associated with each species use, and some potential criteria to develop a suitable model.

Geographical Variability in CYP1B1 Mutations in Primary Congenital Glaucoma.

Primary congenital glaucoma (PCG) is a rare type of glaucoma that is inherited in an autosomal recessive manner. PCG can lead to blindness if not detected early in children aged 3 or younger. PCG varies in presentation among various populations, where disease presentation and disease severity vary by mutation. The most common gene implicated in PCG is cytochrome p450 1B1 (CYP1B1). Here, we sought to review the literature for mutations in CYP1B1 and their presentation among different populations. Areas of interest include recent findings on disease presentation and potential implications on our understanding of PCG pathophysiology.

Posterior Embryotoxon Revisited: An Immunohistologic Study.

PURPOSE: This series describes the immunopathologic features of posterior embryotoxon (PE) and demonstrates that it is not an anterior displaced Schwalbe's line as commonly described, but a peripheral corneal stromal nub variable in location with abnormal extracellular matrix. DESIGN: Case series. PARTICIPANTS: Archived specimens from patients with PE. METHODS: Sections from archived formalin-fixed, paraffin-embedded specimens (n = 9; 7 autopsy and 2 trabeculectomy specimens) were examined by light microscopy. Immunohistochemistry was performed on 5 specimens to characterize the extracellular matrix composition of PE. RESULTS: Posterior embryotoxon appeared as nubs of whorled collagen extending from the corneal stroma, lined in some instances, by Descemet membrane. These nubs were located anterior to Schwalbe's line (n = 4), posteriorly (n = 1), partially embedded in the trabecular meshwork (n = 1), or at Schwalbe's line (n = 2). Qualitatively, collagen I labeling of the PE stroma was similar or weaker than the corneal stroma, whereas collagen III staining was focal and slightly more intense compared with the corneal stroma. Lumican and keratan sulfate staining was similar or less intense in PE compared with the corneal stroma. MAIN OUTCOME MEASURES: Identify location of PE and its immunohistochemical features. CONCLUSIONS: In contrast to the widely accepted definition of PE as a prominent, anteriorly displaced Schwalbe line, histologic evidence suggests that it is a direct extension of the corneal stroma with variable locations that may displace the attenuated Descemet membrane when located anterior to or at Schwalbe's line. Immunohistochemical examination revealed that the composition of PE's extracellular matrix was similar to corneal stroma but with some variability in staining intensity.

Novel serum proteomic signatures in a non-human primate model of retinal injury.

PURPOSE: To identify candidate protein biomarkers in sera indicative of acute retinal injury. METHODS: We used laser photocoagulation as a model of acute retinal injury in Rhesus macaques. In a paired-control study design, we collected serum from each animal (n=6) at 4 h, 1 day, and 3 days following a mock procedure and then again following retinal laser treatment that produced mild lesions. Samples were fractionated by isoelectric focusing, digested with trypsin, and analyzed by liquid chromatography/tandem mass spectrometry (LC-MS/MS). Spectral counting was used to determine relative protein abundances and identify proteins with statistically significant differences between control and treated sera. RESULTS: Mild retinal injury was confirmed by fundus photography and histological examination. The average number of total proteins detected by LC-MS/MS was 908±82 among samples from all three time points. Following statistical analysis and employing stringent filtering criteria, a total of 19 proteins were identified as being significantly more abundant in sera following laser-induced retinal injury, relative to control sera. Many of the proteins detected were unique to one time point. However, four proteins (phosphoglycerate kinase 1, keratin 18, Lewis alpha-3-fucosyltransferase, and ephrin receptor A2) showed differences that were significant at both 4 h and 1 day after laser treatment, followed by a decrease to baseline levels by day 3. CONCLUSIONS: A serum biomarker response to mild retinal laser injury was demonstrated in a primate model. Among the proteins detected with highest significant differences, most are upregulated within 24 h, and their appearance in the serum is transient. It is conceivable that a panel of these proteins could provide a means for detecting the acute-phase response to retinal injury. Further investigation of these candidate biomarkers and their correlation to retinal damage is warranted.

Identification of differentially expressed proteins in the aqueous humor of primary congenital glaucoma.

Primary Congenital Glaucoma (PCG) is an autosomal recessive disease caused by an abnormal development of the anterior chamber angle. Although, PCG has been linked to several genetic loci, the role that the genes at these loci or their encoded proteins play in the pathophysiology of PCG and development of the anterior chamber is not known. To identify proteins that may be altered in PCG and that may help in understanding the underlying pathophysiology of the disease, we took a global proteomics approach. Tryptic digests of the complex mixtures of proteins in aqueous humor were analyzed using Liquid Chromatography/Mass Spectrometry (LC-MS/MS). Proteins were identified by searching the data against the human subset of the UniProt database. The proteomes of aqueous humor in PCG (n = 7) and patients undergoing cataract surgery as control (n = 4) were compared based on the scan counts of comparable proteins. Using stringent filtering criteria, Apolipoprotein A-IV (APOA-IV), Albumin and Antithrombin 3 (ANT3) were detected at significantly higher levels in PCG AH compared to control, whereas Transthyretin (TTR), Prostaglandin-H2 D-isomerase (PTGDS), Opticin (OPT) and Interphotoreceptor Retinoid Binding Protein (IRBP) were detected at significantly lower levels. Many of these proteins play a role in retinoic acid (RA) binding/transport and have been implicated in the pathogenesis of neurodegenerative diseases such as Alzheimer's (AD). It is possible that similar to AD, the pathologic changes in PCG during development could be influenced by the availability of RA in the anterior chamber.

Absence of Cytochrome P450-1b1 Increases Susceptibility of Pressure-Induced Axonopathy in the Murine Retinal Projection.

Mutations in the cytochrome P450-1B1 (Cyp1b1) gene is a common genetic predisposition associated with various human glaucomas, most prominently in primary congenital glaucoma (PCG). The role of Cyp1b1 in the eye is largely unknown, however, its absence appears to drive the maldevelopment of anterior eye structures responsible for aqueous fluid drainage in murine models. Nevertheless, vision loss in glaucoma ultimately results from the structural and functional loss of retinal ganglion cells (RGCs). Cyp1b1's influence in the development and support of retinal ganglion cell structure and function under normal conditions or during stress, such as elevated ocular pressure; the most common risk factor in glaucoma, remains grossly unknown. Thus, to determine the role of Cyp1b1 in normal retinal projection development we first assessed the strucutrual integrity of RGCs in the retina, optic nerve, and superior colliculus in un-manipulated (naïve) Cyp1b1-knockout (Cyp1b1-/-) mice. In addition, in a separate cohort of Cyp1b1-/- and wildtype mice, we elevated and maintained intraocular pressure (IOP) at glaucomatous levels for 5-weeks, after which we compared RGC density, node of Ranvier morphology, and axonal transport between the genotypes. Our results demonstrate that naïve Cyp1b1-/- mice develop an anatomically intact retinal projection absent of overt glaucomatous pathology. Following pressure elevation, Cyp1b1-/- accelerated degradation of axonal transport from the retina to the superior colliculus and altered morphology of the nodes of Ranvier and adjacent paranodes in the optic nerves. Together this data suggests the absence Cyp1b1 expression alone is insufficient to drive murine glaucomatous pathology, however, may increase the vulnerability of retinal axons to disease relevant elevations in IOP.

Analysis of anomalous head posturing in patients with infantile nystagmus syndrome.

PURPOSE: To investigate anomalous head posturing in patients with INS. METHODS: This was a prospective, cohort analysis of clinical and anomalous head posture (AHP) data in 34 patients with INS and an AHP. Particular outcome measures included measurement of AHP in three dimensions of pitch (anterior posterior flexion/extension), yaw (lateral rotation), and roll (lateral flexion) during best-corrected binocular acuity testing and during their subjective sense of straight. Patients were also queried as to their subjective sense of head posture in forced straight position and in their preferred AHP. The paired t test was used to determine significance in differences between measures. RESULTS: A total of 34 patients (19 males [56%]) 9-56 years of age (mean, 16.5 ± 6) were included. Associated systemic or ocular system deficits were present in 30 patients (88%). AHP during best-corrected visual acuity testing averaged 16.5° ± 8.20° (range, 10°-51°), which was significantly different from the mean voluntary "comfortable" position only in the pitch and roll directions (P < 0.001). There was a significant noncongruous response during subjective response to head posturing with most sensing their head as "crooked" (76.5%) when manually straightened (P = 0.001). CONCLUSIONS: The clinical AHP of patients with INS exists in all three spatial dimensions of pitch, yaw, and roll. Although the visual system may be causally related to the onset, amount, and direction of a compensatory AHP in patients with INS, its persistence over time or after surgical intervention is likely due to a combination of visual system (eg, nystagmus, strabismus) and nonvisual system (egocentric and musculo-skeletal) factors.

Prevalence and Clinical Characteristics of Childhood Glaucoma at a Tertiary Care Children's Hospital.

PRECIS: Glaucoma suspect was the most prevalent category in this study followed by glaucoma associated with acquired ocular anomaly and juvenile open-angle glaucoma. Primary congenital glaucoma was diagnosed in only 3% of the population studied. PURPOSE: To describe the prevalence and clinical characteristics of childhood glaucoma diagnosed over a 10-year period among patients aged 18 years or below who were seen at a tertiary care children's hospital using the new Childhood Glaucoma Research Network classification system. METHODS: Medical records of all patients aged 18 years or below (n=108) who were diagnosed with glaucoma between January 1, 2008 through September 30, 2018 were reviewed. Data collected included demographics (age at diagnosis, sex, and family history of glaucoma), intraocular pressure, disc-to-cup ratio, retinal nerve fiber layer thickness, and refractive errors. Clinical characteristics of each patient were evaluated according to the criteria established by Childhood Glaucoma Research Network. Categorical distributional equivalence comparisons were performed using the Pearson χ test. A P-value <0.05 was defined as statistically significant. RESULTS: A total of 108 patients with a diagnosis of childhood glaucoma or glaucoma suspect were included in this study. Sixty-four percent of these patients were males (P<0.0001). The mean age at the time of diagnosis was 7.07±5.4 years. "Glaucoma suspect" was the most prevalent category (46%, P=0.0002), followed by glaucoma associated with the acquired ocular anomaly (20%) and juvenile open-angle glaucoma (16%). Primary congenital glaucoma represented 3% and all these patients were males. Sixty-nine percent of the patients had bilateral involvement (P=0.0073). The highest intraocular pressure recorded in the study was 57 mm Hg, the largest cup-to-disc ratio was 0.96, and the lowest retinal nerve fiber layer measurement was 39 µm. Ninety-two percent of the patients had refractive errors and 85% of them had astigmatism. CONCLUSIONS: Establishing a pattern and the associated clinical characteristics of childhood glaucoma at tertiary care children's hospitals will help in developing collaborative research efforts and effective treatment/management strategies for children with these rare groups of disorders.

Long-term Outcomes of Baerveldt Glaucoma Implant Shunts as a Primary Versus Secondary Procedure.

PURPOSE: To determine the 5-year success rate for Baerveldt glaucoma implant (BGI) in patients who received the implant as a primary (primary BGI, used as the initial surgical procedure) or secondary (secondary BGI, used after trabeculectomy) by a single surgeon between year 1994 and 2010. PATIENTS AND METHODS: A total of 117 eyes from patients who underwent BGI placement as a primary or secondary procedure were included in this study. Demographics, previous history, type of glaucoma, intraocular pressure (IOP), visual acuity (VA), glaucoma medication use, and early and late postoperative complications were collected. Postoperative data were collected at day 1, 30, 60, and every year until the last visit (minimum of 2 y). IOP was the main outcome measure. Secondary outcome measures included VA, glaucoma medication use, and early and late postoperative complications. Overall success rates were calculated for primary and secondary BGI using Kaplan-Meier survival analysis. Differences between survival curves were determined using log-rank test. Risk factors for success were defined by Cox proportional-hazards regression model. RESULTS: At the 5-year follow-up, the overall success rates (determined as IOP between 6 and 21 mm Hg) in the primary and secondary BGI were 58% (49/79) and 53% (20/38), respectively (P=0.56). The overall success rate dropped by an average 10% and 13% per year for the primary and secondary BGI groups, respectively (P=0.05). The complete success rates at the 5-year follow-up for primary and secondary BGI were 24% (19/79) and 13% (5/38), respectively, whereas the qualified success rates were 34% (27/79) and 39% (15/38), respectively. There was a significant decrease in IOP [from 31.23 (±9.51) to 12.86 (±4.84) mm Hg (P<0.001) for the primary BGI group, and from 26.35 (±7.22) to 13.92 (±5.90) mm Hg (P<0.001) for the secondary BGI group]. There was also a significant drop in medication use but a significant worsening in VA in both groups (P<0.05) likely from cataract. The difference in the incidence of postoperative complications was not statistically significant between the groups. CONCLUSIONS: Although, the success rates were similar for the primary and secondary BGI at the 5-year follow-up, the drop in the success rate per year was significantly higher in the secondary BGI group. In contrast, both procedures had similar incidence of postoperative complications.

Non-invasive Detection of Unique Molecular Signatures in Laser-Induced Retinal Injuries.

Unintentional laser exposure is an increasing concern in many operational environments. Determining whether a laser exposure event caused a retinal injury currently requires medical expertise and specialized equipment that are not always readily available. The purpose of this study is to test the feasibility of using dynamic light scattering (DLS) to non-invasively detect laser retinal injuries through interrogation of the vitreous humor (VH). Three grades of retinal laser lesions were studied: mild (minimally visible lesions), moderate (Grade II), and severe (Grade III). A pre-post-treatment design was used to collect DLS measurements in vivo at various time points, using a customized instrument. VH samples were analyzed by liquid chromatography/tandem mass spectrometry (LC-MS/MS) and relative protein abundances were determined by spectral counting. DLS signal analysis revealed significant changes in particle diameter and intensity in laser-treated groups as compared with control. Differences in protein profile in the VH of the laser-treated eyes were noted when compared with control. These results suggest that laser injury to the retina induces upregulation of proteins that diffuse into the VH from the damaged tissue, which can be detected non-invasively using DLS.

Differential Expression of Vitreous Proteins in Young and Mature New Zealand White Rabbits.

Different anatomical regions have been defined in the vitreous humor including central vitreous, basal vitreous, vitreous cortex, vitreoretinal interface and zonule. In this study we sought to characterize changes in the proteome of vitreous humor (VH) related to compartments or age in New Zealand white rabbits (NZW). Vitreous humor was cryo-collected from young and mature New Zealand white rabbit eyes, and dissected into anterior and posterior compartments. All samples were divided into 4 groups: Young Anterior (YA), Young Posterior (YP), Mature Anterior (MA) and Mature Posterior (MP) vitreous. Tryptic digests of total proteins were analyzed by liquid chromatography followed by tandem mass spectrometry. Spectral count was used to determine the relative protein abundances and identify proteins with statistical differences between compartment and age groups. Western blotting was performed to validate some of the differentially expressed proteins. Our results showed that 231, 375, 273 and 353 proteins were identified in the YA, YP, MA and MP respectively. Fifteen proteins were significantly differentially expressed between YA and YP, and 11 between MA and MP. Carbonic anhydrase III, lambda crystallin, alpha crystallin A and B, beta crystallin B1 and B2 were more abundant in the anterior region, whereas vimentin was less abundant in the anterior region. For comparisons between age groups, 4 proteins were differentially expressed in both YA relative to MA and YP relative to MP. Western blotting confirmed the differential expression of carbonic anhydrase III, alpha crystallin B and beta crystallin B2. The protein profiles of the vitreous humor showed age- and compartment-related differences. This differential protein profile provides a baseline for understanding the vitreous compartmentalization in the rabbit and suggests that further studies profiling proteins in different compartments of the vitreous in other species may be warranted.

Postmortem vitreous bevacizumab levels of an infant treated for retinopathy of prematurity.

We report the vitreous concentration of bevacizumab after injection for the treatment of retinopathy of prematurity (ROP). A premature neonate diagnosed with type 1 ROP was treated in both eyes with 0.625 mg intravitreal bevacizumab injection at 32 weeks' postconceptual age. Eleven weeks later there was complete regression clinically, but the patient died. Vitreous samples taken at autopsy revealed a bevacizumab vitreous concentration of 41.57 ng/ml. Histopathology of the retina showed residual preretinal neovascularization. Bevacizumab elimination from the infant vitreous is similar to that of adults, and, although complete regression was clinically apparent, it was not confirmed histopathologically.

Assessment of alkoxylphenacyl-based polycarbonates as a potential platform for controlled delivery of a model anti-glaucoma drug.

Treatment strategies for glaucoma will benefit from injectable and/or implantable delivery systems that can achieve sustained delivery of neuroprotective agents (to the posterior segment) and/or intraocular pressure lowering drugs (to the anterior segment). In this regard, we have evaluated the suitability of a new polymer (alkoxylphenacyl-based polycarbonates copolymer with polycaprolactone; AP-PCL 20% w/w) as a platform for ocular drug delivery. Brimonidine tartrate (BRT) was applied as a model anti-glaucoma drug. The polymer was applied to develop injectable (nanoparticles) and implantable (microfilms) delivery systems. Nanoparticles fabricated from AP-PCL were stable and have an average size less than 200nm. The AP-PCL microfilms prepared by compression molding showed a gradual hydrolytic in-vitro degradation monitored by water uptake, weight loss, microscopy, DSC and FT-IR measurements. AP-PCL microfilms achieve sustained delivery of BRT for up to 90days. Biocompatibility of AP-PCL-based delivery systems was demonstrated from studies in human trabecular meshwork cell line as well as after intravitreal injections in rats. The overall trend demonstrated that AP-PCL delivery systems may be considered as suitable candidates for prolonged drug delivery in chronic ocular disorders such as glaucoma.