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Although the visual system extends through the brain, most vision loss originates from defects in the eye. Its central element is the neural retina, which senses light, processes visual signals, and transmits them to the rest of the brain through the optic nerve (ON). Surrounding the retina are numerous other structures, conventionally divided into anterior and posterior segments. Here we used high-throughput single nucleus RNA sequencing (snRNA-seq) to classify and characterize cells in the extraretinal components of the posterior segment: ON, optic nerve head (ONH), peripheral sclera, peripapillary sclera (PPS), choroid, and retinal pigment epithelium (RPE). Defects in each of these tissues are associated with blinding diseases – for example, glaucoma (ONH and PPS), optic neuritis (ON), retinitis pigmentosa (RPE), and age-related macular degeneration (RPE and choroid). From ∼151,000 single nuclei, we identified 37 transcriptomically distinct cell types, including multiple types of astrocytes, oligodendrocytes, fibroblasts, and vascular endothelial cells. Our analyses revealed a differential distribution of many cell types among distinct structures. Together with our previous analyses of the anterior segment and retina, the new data complete a “Version 1” cell atlas of the human eye. We used this atlas to map the expression of >180 genes associated with the risk of developing glaucoma, which is known to involve ocular tissues in both anterior and posterior segments as well as neural retina. Similar methods can be used to investigate numerous additional ocular diseases, many of which are currently untreatable.

Increased intraocular pressure (IOP) represents a major risk factor for glaucoma, a prevalent eye disease characterized by death of retinal ganglion cells; lowering IOP is the only proven treatment strategy to delay disease progression. The main determinant of IOP is the equilibrium between production and drainage of aqueous humor, with compromised drainage generally viewed as the primary contributor to dangerous IOP elevations. Drainage occurs through two pathways in the anterior segment of the eye called conventional and uveoscleral. To gain insights into the cell types that comprise these pathways, we used high-throughput single-cell RNA sequencing (scRNAseq). From ∼24,000 single-cell transcriptomes, we identified 19 cell types with molecular markers for each and used histological methods to localize each type. We then performed similar analyses on four organisms used for experimental studies of IOP dynamics and glaucoma: cynomolgus macaque ( Macaca fascicularis ), rhesus macaque ( Macaca mulatta ), pig ( Sus scrofa ), and mouse ( Mus musculus ). Many human cell types had counterparts in these models, but differences in cell types and gene expression were evident. Finally, we identified the cell types that express genes implicated in glaucoma in all five species. Together, our results provide foundations for investigating the pathogenesis of glaucoma and for using model systems to assess mechanisms and potential interventions.

ZusammenfassungDas Glaukom ist eine neurodegenerative Erkrankung, die mit der Zeit zu irreversibler Erblindung führt. Als bestimmendes Merkmal hier gilt der Verlust von retinalen Ganglienzellen (RGZ) im Auge und ihrer Axone im Sehnerv. Ein erhöhter Augeninnendruck (intraokularer Druck, IOD) gilt als Hauptrisikofaktor für die Entstehung eines Glaukoms, jedoch zeigt sich, dass dieser weder notwendig noch ausreichend für die Entstehung und das Fortschreiten der Erkrankung ist. Dies hat die Forschung und Entwicklung neuer Strategien zur Erkennung und Behandlung von Glaukomen mit dem Schwerpunkt auf Neuroprotektion – dem Schutz von RGZs vor dem Sterben – motiviert. Zusätzlich ist es im Bereich der Diagnose und Behandlung durch eine Reduktion des IOD in den letzten Jahren zur Entwicklung neuer Herangehensweisen gekommen. Dieser Artikel gibt einen Überblick über die zurzeit gängigen Theorien der pathophysiologischen Mechanismen, die einer Entstehung eines Glaukoms zugrunde liegen, sowie neuester Forschungsbemühungen mit Fokus auf Neuroprotektion und aktueller präklinischer und klinischer Studien, um eine Diagnose und Therapie des Glaukoms zu verbessern.

The anterior segment of the eye consists of the cornea, iris, ciliary body, crystalline lens and aqueous humor outflow pathways. Together, these tissues are essential for the proper functioning of the eye. Disorders of vision have been ascribed to defects in all of them; some, including glaucoma and cataract, are among the most prevalent causes of blindness in the world. To characterize the cell types that comprise these tissues, we generated an anterior segment cell atlas of the human eye using high throughput single-nucleus RNA sequencing (snRNAseq). We profiled 191,992 nuclei from non-diseased anterior segment tissues from 6 human donors, identifying >60 cell types. Many of these cell types were discrete, whereas others, especially in lens and cornea, formed continua corresponding to known developmental transitions that persist in adulthood. Having profiled each tissue separately, we performed an integrated analysis of the entire anterior segment revealing that some cell types are unique to single structure whereas others are shared across tissues. The integrated cell atlas was then used to investigate cell type-specific expression patterns of more than 900 human ocular disease genes identified either through Mendelian inheritance patterns or genome-wide association studies (GWAS).SIGNIFICANCE STATEMENTSeveral of the most prevalent blinding ocular conditions worldwide, including glaucoma, cataract and uncorrected refractive error, involve structures of the anterior segment of the human eye, which consists of the cornea, iris, ciliary body, crystalline lens and aqueous humor outflow pathways. In addition to providing transcriptomic profiles of the cell types within individual tissues, this work contributes to our understanding of the relatedness and diversity of these cell types across contiguous tissues by generating an integrated anterior segment cell atlas and documenting the expression of over 900 disease-associated genes in each cell type. By allowing simultaneous interrogation of cell-type specific expression of genes across multiple tissues, the atlas may yield broad insight into normal and disease-associated anterior segment functions.

Glaucoma is a leading cause of blindness. Current glaucoma medications work by lowering intraocular pressure (IOP), a risk factor for glaucoma, but most treatments do not directly target the pathological changes leading to increased IOP, which can manifest as medication resistance as disease progresses. To identify physiological modulators of IOP, we performed genome- and exome-wide association analysis in >129,000 individuals with IOP measurements and extended these findings to an analysis of glaucoma risk. We report the identification and functional characterization of rare coding variants (including loss-of-function variants) in ANGPTL7 associated with reduction in IOP and glaucoma protection. We validated the human genetics findings in mice by establishing that Angptl7 knockout mice have lower (~2 mmHg) basal IOP compared to wild-type, with a trend towards lower IOP also in heterozygotes. Conversely, increasing mAngptl7 levels via injection into mouse eyes increases the IOP. We also show that acute gene silencing via siRNA knockdown of Angptl7 in adult mice lowers the IOP (~2-4 mmHg), reproducing the observations in knockout mice. Collectively, our data suggest that ANGPTL7 is important for IOP homeostasis and is amenable to therapeutic modulation to help maintain a healthy IOP that can prevent onset or slow the progression of glaucoma.

Purpose To characterize the visual outcomes and the treatment course of patients with exudative age-related macular degeneration (AMD) based on ocular hypotensive use. Design A matched retrospective cohort study of patients enrolled in Kaiser Permanente Southern California health plan was conducted. Patients taking ocular hypotensives were identified using pharmacy dispensing data and were matched to controls to compare visual acuity, number of anti-VEGF injections, and conversation to secondary anti-VEGF agents in the first year of treatment. Subgroup analysis was performed based on the number of ocular hypotensive agents (0, 1, 2 or 3+ agents) and drug class (aqueous suppressants and prostaglandin analogs). Results A total of 234 patients patients were examined. Baseline and final visual acuity did not significantly differ between drop users and controls, including on subgroup analysis. The average number of anti-VEGF injections did not differ between drop users and controls (6.1 vs 6.2, p=0.97), nor did the percentage of patients who were switched to a second-line anti-VEGF agent (23.9% vs 17.9%, p=0.26). Subgroup analysis did not reveal significant differences in the number of anti-VEGF injections and the percentage of patients switched to secondary agents, with patients receiving 6 ±1 injections across regardless of the number or class of ocular hypotensive agents used. Conclusion Patients with concurrent glaucoma and exudative AMD have similar visual outcomes and treatment courses compared to those not taking ocular hypotensives. Although aqueous suppressants have been suggested to prolong anti-VEGF residence time, patients using these agents did not demonstrate visual benefit or a reduced injection burden in this series.

Purpose:This study examines treatment-based outcomes of endophthalmitis due to antivascular endothelial growth factor (anti-VEGF) intravitreal injection and its effect on subsequent management of neovascular disease.Methods:A retrospective multicenter study was conducted of 157 patients with a diagnosis of endophthalmitis following anti-VEGF intravitreal injection at 10 major ophthalmic centers.Results:The median number of injections before endophthalmitis was 10 (range, 1 to 84 injections). Initial treatment with tap and inject with or without subsequent vitrectomy trended toward smaller visual acuity changes from baseline (4 ETDRS [Early Treatment Diabetic Retinopathy Study] letter difference vs 19 ETDRS letter difference) compared with initial vitrectomy, but the difference was not statistically significant. There was no significant change in medication choice among injections after endophthalmitis. There was a statistically significant shift away from regular interval (1- to 2-month) injections and a shift toward treat-and-extend and as-needed injection algorithms.Conclusions:The visual outcomes were not significantly different between patients who initially underwent tap and injection of antibiotics and those who underwent vitrectomy. There was no significant change in medication choice before and after endophthalmitis but there was a shift toward lower-frequency injection algorithms after postintravitreal injection endophthalmitis compared with prior.

Purpose To ascertain the incidence of unexpected management changes at the postoperative week 1 visit in asymptomatic patients who have had an uncomplicated cataract surgery and a routine postoperative day 1 examination. Design Retrospective observational study. Methods A retrospective chart review was conducted of all cases of cataract extraction by phacoemulsification with intraocular lens insertion performed by the Comprehensive Ophthalmology Service at Massachusetts Eye and Ear between January 1, 2014 and December 31, 2014. The preoperative consultation, operative report, and postoperative day 1 and week 1 (postoperative days 5-14) visits were reviewed. Cases with intraoperative complications, as well as clinical findings at postoperative day 1 requiring close follow-up, were excluded. The main outcome measure was incidence of unexpected management changes at the postoperative week 1 visit after cataract surgery, defined as an unanticipated change in postoperative drops, additional procedures, or urgent referral to a specialty service. Results Overall, 1938 surgical cases of 1471 patients were reviewed, and 1510 cases (77.9%) underwent uncomplicated phacoemulsification with intraocular lens implantation with a routine postoperative day 1 examination. Of these 1510 cases, 238 (15.8%) reported symptoms at the postoperative week 1 visit, including flashes, floaters, redness, pain, or decreased vision, which warranted an examination. In total, 1272 cases were asymptomatic, and only 11 of these cases (0.9%) had an unexpected management change at postoperative week 1. Eight of 11 patients were asymptomatic steroid responders requiring alteration of their postoperative drops. Two of these patients had an intraocular pressure >30 mm Hg. Conclusions Unexpected management changes at the postoperative week 1 timepoint after cataract surgery are rare in asymptomatic patients who have had uncomplicated cataract surgery and a routine postoperative day 1 examination. Limited data are available to outline an optimal postoperative regimen after cataract surgery. The results of this study suggest that postoperative week 1 examinations could potentially be performed on an as-needed basis in the appropriate subgroup of patients after cataract surgery.

A 20-year-old woman was referred to the neuro-ophthalmology clinic at Beth Israel Deaconess Medical Center for evaluation of diplopia. Three months prior to presentation, she awoke with oblique binocular diplopia, which resolved spontaneously over a period of several weeks but recurred 1 month prior to presentation, accompanied by an inability to make facial expressions on her left side and difficulty with eye movements. She denied diplopia in primary gaze but complained of horizontal diplopia in right- and leftward gaze, worse in left gaze. She denied eye pain and any change in visual acuity. Associated symptoms included dry eye on the left, for which she was applying artificial tears four times daily and lubricating ointment at bedtime. She was previously healthy and took no medications. Family history was unremarkable. She had no history of head or eye trauma.

Most irreversible blindness results from retinal disease. To advance our understanding of the etiology of blinding diseases, we used single-cell RNA-sequencing (scRNA-seq) to analyze the transcriptomes of ∼85,000 cells from the fovea and peripheral retina of seven adult human donors. Utilizing computational methods, we identified 58 cell types within 6 classes: photoreceptor, horizontal, bipolar, amacrine, retinal ganglion and non-neuronal cells. Nearly all types are shared between the two retinal regions, but there are notable differences in gene expression and proportions between foveal and peripheral cohorts of shared types. We then used the human retinal atlas to map expression of 636 genes implicated as causes of or risk factors for blinding diseases. Many are expressed in striking cell class-, type-, or region-specific patterns. Finally, we compared gene expression signatures of cell types between human and the cynomolgus macaque monkey, Macaca fascicularis. We show that over 90% of human types correspond transcriptomically to those previously identified in macaque, and that expression of disease-related genes is largely conserved between the two species. These results validate the use of the macaque for modeling blinding disease, and provide a foundation for investigating molecular mechanisms underlying visual processing.

Purpose To describe the characteristics and outcomes of endogenous endophthalmitis. Design Retrospective case series. Participants Patients with endogenous endophthalmitis. Methods A retrospective chart review of patients diagnosed with endogenous endophthalmitis between September 1, 2006, and November 1, 2014. Main Outcome Measures Clinical findings, treatments, microbial results, visual outcomes, and secondary ocular sequelae. Results Sixty-three patients (68 eyes) were diagnosed with endogenous endophthalmitis. Ocular symptoms were the first manifestation of disease in 76% of patients. Fungal and bacterial endophthalmitis were seen in 37% (n = 25) and 43% (n = 29) of eyes, respectively. In 47% of eyes (n = 32), the disease was associated with intravenous drug use. Eighteen percent of eyes (n = 12) underwent an initial pars plana vitrectomy (PPV) with intravitreal antibiotics, none of which required a secondary intervention for acute infection. Four percent of eyes (n = 3) received only systemic treatment. Seventy-eight percent of eyes (n = 53) underwent initial bedside aspirate with intravitreal injection of antibiotics (tap-and-injection), of which 55% (n = 29) required a secondary PPV. Of eyes that underwent secondary PPV after initially negative culture results from the tap-and-injection, 52% demonstrated positive culture results at the time of secondary PPV (n = 11/21) despite all but 1 having received appropriate antimicrobial coverage initially. Fifty-four percent of eyes (n = 37) experienced secondary ocular sequelae. Eyes that received initial tap-and-injection had statistically nonsignificant better average initial vision, but worse average vision at each follow-up interval, compared to PPV while being less likely to gain 2 lines or more of vision at every follow-up interval except 6 months, with the difference reaching statistical significance at 1 week (odds ratio = 0.014; P = 0.037). Eyes that underwent initial tap-and-injection were statistically significantly more likely to require a secondary PPV (55% vs. 0%; P = 0.0006) and had fewer positive microbial results (19% vs. 67%) than those that underwent initial PPV (P = 0.002). Conclusions Most eyes that received initial tap-and-injection eventually underwent a secondary PPV. Initial PPV may have an important role in management because it was associated with better diagnostic yield and a trend toward better visual outcomes.

Fresh trabecular meshwork tissue is dissected from post-mortem human eyes and dissociated into a single cell suspension.

Glaucoma is a neurodegenerative disease that leads to irreversible blindness over time. Its defining feature is the loss of retinal ganglion cells (RGCs) in the eye and their axons in the optic nerve. Increased intraocular pressure (IOP) is a major risk factor for the development of glaucoma, but is neither necessary nor sufficient for the disease and its progression; this motivates research and development of new strategies for the detection and treatment of glaucoma that focus on neuroprotection - protection of RGCs from dying. In addition, for diagnosis and treatment by reducing IOP, new approaches have been developed in recent years. This article reviews current theories of pathophysiological mechanisms underlying glaucoma and recent research - with a focus on neuroprotection and current preclinical and clinical studies to improve the diagnosis and treatment of glaucoma.Das Glaukom ist eine neurodegenerative Erkrankung, die mit der Zeit zu irreversibler Erblindung führt. Als bestimmendes Merkmal hier gilt der Verlust von retinalen Ganglienzellen (RGZ) im Auge und ihrer Axone im Sehnerv. Ein erhöhter Augeninnendruck (intraokularer Druck, IOD) gilt als Hauptrisikofaktor für die Entstehung eines Glaukoms, jedoch zeigt sich, dass dieser weder notwendig noch ausreichend für die Entstehung und das Fortschreiten der Erkrankung ist. Dies hat die Forschung und Entwicklung neuer Strategien zur Erkennung und Behandlung von Glaukomen mit dem Schwerpunkt auf Neuroprotektion – dem Schutz von RGZs vor dem Sterben – motiviert. Zusätzlich ist es im Bereich der Diagnose und Behandlung durch eine Reduktion des IOD in den letzten Jahren zur Entwicklung neuer Herangehensweisen gekommen. Dieser Artikel gibt einen Überblick über die zurzeit gängigen Theorien der pathophysiologischen Mechanismen, die einer Entstehung eines Glaukoms zugrunde liegen, sowie neuester Forschungsbemühungen mit Fokus auf Neuroprotektion und aktueller präklinischer und klinischer Studien, um eine Diagnose und Therapie des Glaukoms zu verbessern.

Introduction. Pozelimab (REGN3918) and cemdisiran (ALN-CC5) are C5 inhibitors under development for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), myasthenia gravis (MG), and other diseases in which tissue damage is mediated by terminal complement pathway activity. Pozelimab is a fully human monoclonal immunoglobulin G4P (IgG4P) antibody directed against C5, and cemdisiran is a synthetic small interfering RNA (siRNA) targeting C5 mRNA. Both agents can be administered via subcutaneous (SC) injection. Pharmacokinetic (PK)/pharmacodynamic (PD) modeling based on observed data from both pozelimab and cemdisiran healthy volunteer studies (NCT03115996, NCT02352493) suggests that, by combining cemdisiran and pozelimab, the dose of both agents may be significantly reduced and the interval for SC dosing of pozelimab may be significantly increased. Objectives. To provide initial safety and tolerability data for a SC cemdisiran/pozelimab combination approach. Methods. This is an ongoing phase 1, open-label, parallel-dose cohort combination study (NCT04601844) assessing the safety and tolerability of ascending doses of SC pozelimab in combination with SC cemdisiran when administered on the same day or sequentially, on different days, in healthy subjects. Cohort Descriptions. Three parallel ascending-dose cohorts, consisting of six subjects each, were selected based on PK/PD modeling using observed data from both pozelimab and cemdisiran non-combination healthy volunteer studies: Cohort 1: Cemdisiran low dose SC followed by pozelimab low dose SC, administered on different days Cohort 2: Cemdisiran high dose SC followed by pozelimab low dose SC, administered on different days Cohort 3: Cemdisiran high dose SC and pozelimab high dose SC, both administered on the same day Dose regimens were designed to limit the duration of >50% complement inhibition for no longer than 8 weeks, to mitigate risk in the enrolled healthy subjects. An optional additional Cohort 4 was included in the study design and this interim analysis was planned to review safety data to guide the decision regarding whether to enroll this cohort and to inform its dose selection. Interim Analysis: An interim safety analysis was performed with a data cut-off corresponding to study day 127 for Cohort 1, study day 85 for Cohort 2, and study day 71 for Cohort 3. Eighteen healthy volunteer subjects, nine female and nine male, with a mean age of 36 years (standard deviation 9.5 years), were randomized to one of the three cohorts. Demographic and baseline characteristics were comparable for subjects in each cohort. A total of 47 treatment emergent adverse events (TEAEs) were reported, with comparable distribution across cohorts, all mild to moderate in severity with no severe TEAEs. "Nervous system disorders" was the TEAE System Organ Class with the most subjects for all three cohorts, occurring in 12 (66.7%) of the 18 subjects. "Headache" was the most frequent MedDRA Preferred Term for all three cohorts, occurring in 11 (61.1%) of the 18 subjects. All TEAEs were recovered or recovering at the time of data cut-off, and there were no study drug discontinuations or interruptions of treatment due to TEAEs. There were no serious TEAEs or deaths. There were no clinically meaningful findings or treatment-emergent changes reported on the vital signs or laboratory safety tests. Conclusions: The combined SC administration of pozelimab and cemdisiran represents a promising approach to achieve therapeutically significant complement inhibition for extended durations. An interim safety analysis demonstrated that the combined administration was generally safe and well tolerated. Final PK/PD analysis from this healthy volunteer study will allow for assessment of agreement between modeling predictions and observed data, and further inform combination dose regimens for studies in target patient populations. Disclosures van Zyl: Regeneron Pharmaceuticals, Inc.: Current Employment. Weyne: Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Chaudhari: Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Harari: Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Levy: Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Miller: Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Chen: Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Meagher: Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Rodgers: Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Perlee: Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Morton: Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Weinreich: Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company. Yancopoulos: Regeneron Pharmaceuticals, Inc.: Current Employment, Current holder of stock options in a privately-held company.

Proliferative diabetic retinopathy (PDR) is a common cause of blindness in the developed world’s working adult population and affects those with type 1 and type 2 diabetes. We identified Runt-related transcription factor 1 (RUNX1) as a gene upregulated in CD31+ vascular endothelial cells obtained from human PDR fibrovascular membranes (FVMs) via transcriptomic analysis. In vitro studies using human retinal microvascular endothelial cells (HRMECs) showed increased RUNX1 RNA and protein expression in response to high glucose, whereas RUNX1 inhibition reduced HRMEC migration, proliferation, and tube formation. Immunohistochemical staining for RUNX1 showed reactivity in vessels of patient-derived FVMs and angiogenic tufts in the retina of mice with oxygen-induced retinopathy, suggesting that RUNX1 upregulation is a hallmark of aberrant retinal angiogenesis. Inhibition of RUNX1 activity with the Ro5–3335 small molecule resulted in a significant reduction of neovascular tufts in oxygen-induced retinopathy, supporting the feasibility of targeting RUNX1 in aberrant retinal angiogenesis.

High-acuity vision in primates, including humans, is mediated by a small central retinal region called the fovea. As more accessible organisms lack a fovea, its specialized function and its dysfunction in ocular diseases remain poorly understood. We used 165,000 single-cell RNA-seq profiles to generate comprehensive cellular taxonomies of macaque fovea and peripheral retina. More than 80% of >60 cell types match between the two regions but exhibit substantial differences in proportions and gene expression, some of which we relate to functional differences. Comparison of macaque retinal types with those of mice reveals that interneuron types are tightly conserved. In contrast, projection neuron types and programs diverge, despite exhibiting conserved transcription factor codes. Key macaque types are conserved in humans, allowing mapping of cell-type and region-specific expression of >190 genes associated with 7 human retinal diseases. Our work provides a framework for comparative single-cell analysis across tissue regions and species. Single-cell-based analysis provides a comprehensive molecular and cellular taxonomy of the primate retina., National Institutes of Health (U.S.) (Grant MH105960), National Institutes of Health (U.S.) (Grant EY025840), National Institutes of Health (U.S.) (Grant EY028633), National Institutes of Health (U.S.) (Grant EY025555), National Institutes of Health (U.S.) (Grant EY028625), BrightFocus Foundation (Grant M2014055)

Purpose To present cases of endophthalmitis following intravitreal injections where povidone-iodine (PI) was not used as part of the surgical preparation. Design Retrospective case series. Methods All cases of presumed injection-related endophthalmitis presenting to the Massachusetts Eye and Ear Infirmary between June 2008 and November 2014 and Dean McGee Eye Institute between January 2010 and January 2015 were identified. Patients who did not receive PI preparation owing to documented self-reported allergy to iodine, iodine-containing contrast material, or shellfish were identified and their injection histories and clinical courses reviewed. Results The combined rate of postinjection endophthalmitis at these 2 centers was 0.019%. Among 42 patients with postinjection endophthalmitis, 5 (11.9%) did not receive PI prophylaxis. The mean number of intravitreal injections without PI before the development of endophthalmitis was 10.6 with a 9.4% rate of endophthalmitis (5 cases per 53 injections). All patients underwent tap-and-inject procedures with vancomycin 1 mg and ceftazidime 2 mg. Two patients did not receive PI at the time of tap and inject; 1 of these patients required subsequent pars plana vitrectomy for worsening clinical course. Cultures were positive in 4 of 5 cases; all positive cultures grew coagulase-negative Staphylococcus . All patients who received subsequent intravitreal injections received PI prophylaxis without allergic reactions, thus demonstrating a lack of true PI allergy. Conclusions Avoiding PI owing to self-reported iodine "allergy" risks substantial ocular morbidity. Allergy testing can be pursued per patient request or in rare cases of suspected true PI allergy; however, in cases where delayed treatment would adversely affect visual outcome, the clinician should feel confident that minimal allergic risk exists.

To describe the characteristics and outcomes of endogenous endophthalmitis.Retrospective case series.Patients with endogenous endophthalmitis.A retrospective chart review of patients diagnosed with endogenous endophthalmitis between September 1, 2006, and November 1, 2014.Clinical findings, treatments, microbial results, visual outcomes, and secondary ocular sequelae.Sixty-three patients (68 eyes) were diagnosed with endogenous endophthalmitis. Ocular symptoms were the first manifestation of disease in 76% of patients. Fungal and bacterial endophthalmitis were seen in 37% (n = 25) and 43% (n = 29) of eyes, respectively. In 47% of eyes (n = 32), the disease was associated with intravenous drug use. Eighteen percent of eyes (n = 12) underwent an initial pars plana vitrectomy (PPV) with intravitreal antibiotics, none of which required a secondary intervention for acute infection. Four percent of eyes (n = 3) received only systemic treatment. Seventy-eight percent of eyes (n = 53) underwent initial bedside aspirate with intravitreal injection of antibiotics (tap-and-injection), of which 55% (n = 29) required a secondary PPV. Of eyes that underwent secondary PPV after initially negative culture results from the tap-and-injection, 52% demonstrated positive culture results at the time of secondary PPV (n = 11/21) despite all but 1 having received appropriate antimicrobial coverage initially. Fifty-four percent of eyes (n = 37) experienced secondary ocular sequelae. Eyes that received initial tap-and-injection had statistically nonsignificant better average initial vision, but worse average vision at each follow-up interval, compared to PPV while being less likely to gain 2 lines or more of vision at every follow-up interval except 6 months, with the difference reaching statistical significance at 1 week (odds ratio = 0.014; P = 0.037). Eyes that underwent initial tap-and-injection were statistically significantly more likely to require a secondary PPV (55% vs. 0%; P = 0.0006) and had fewer positive microbial results (19% vs. 67%) than those that underwent initial PPV (P = 0.002).Most eyes that received initial tap-and-injection eventually underwent a secondary PPV. Initial PPV may have an important role in management because it was associated with better diagnostic yield and a trend toward better visual outcomes.

A 31-year-old man presented with a Zone I open globe injury 2 days after blunt head trauma. Initial exam was significant for a 6.5 mm full thickness corneal wound, Seidel positive without provocation, and ingrowth of blood vessels from the limbus into the wound and surrounding corneal whitening. There were also posterior synechiae and sectoral iris atrophy inferior and posteriorly to the corneal wound suggesting a previous corneal injury at the site of new acute rupture. Intraoperatively the wound bled while suturing and the corneal tissue in this area was friable, consistent with delayed presentation and possible chronic intermittent low-grade inflammation or infection from a previous trauma. Post-operatively, the patient underwent staged suture removal at 6 and 8 weeks, respectively. His final best-corrected visual acuity was 20/20.

A healthy woman in her 40s presented with an open globe injury (OGI) of the left eye due to a penetrating stab wound inflicted by her domestic partner. Exam was significant for a laceration above the left eyebrow, CF vision, no obvious corneal or conjunctival lacerations, a deep anterior chamber compared to fellow eye, a pupil peaked superonasally, vitreous hemorrhage (VH) and retinal elevations concerning for retinal detachment. Surgical exploration confirmed a Zone II-III scleral laceration and a subfascial communication between the periocular space and the supra-brow laceration, which was felt to be the entry site. Social services and intimate partner violence resources were mobilized prior to discharge. Two weeks following the initial OGI repair, she underwent uncomplicated pars plana vitrectomy to clear the VH. No retinal detachments or tears were noted intraoperatively. Her final uncorrected visual acuity was 20/30.

A 63-year-old man presented 10 days following penetrating wood injury to right eye. Exam confirmed a Zone I open globe with lens violation. He underwent primary globe closure immediately. Lens extraction was delayed due to the poor intraocular view from significant corneal edema. Inflammation was controlled medically and cataract extraction without insertion of intraocular lens was performed one month later with the corneal sutures still in place. Secondary intraocular lens implantation versus an aphakic contact lens was offered after the corneal sutures were removed; the patient deferred additional surgery and elected to seek follow-up locally. The patient’s final visual acuity was 20/50 with a +11 diopter lens and pinhole occluder.

A 53 year-old male was assaulted resulting in bilateral open globe ruptures. Post-operatively the left eye remained no light perception and the right eye remained light perception only; at 4 weeks after the initial injury, vitrectomy was attempted to reattach the retina but it was found intraoperatively to be inoperable. The patient expired 3 months later due to unrelated causes.

A 31-year-old man presented with a Zone III open globe injury of the left eye following severe blunt trauma from a hockey stick. The vision was hand motions (HM), intraocular pressure (IOP) was 5, and there was an afferent pupillary defect (APD) by reverse. During surgical exploration, the rupture was identified at the equator, approximately 15 mm posterior to the limbus. The wound ran posterior to the lateral rectus muscle insertion, which was temporarily disinserted to provide adequate exposure for wound closure. Postoperative B-scan revealed a funnel retinal detachment (RD), for which he underwent complex repair with 360 relaxing retinectomy and silicone oil tamponade. On the most recent follow-up, 8 months after injury, his vision was HM, IOP 14, and his remaining retina remained attached under oil.

A 22-year-old man presented with a severe, complex Zone I-II open globe injury of the left eye after a fall. The patient underwent repair of this open globe injury in addition to associated facial lacerations. The patient’s postoperative course was complicated by a funnel retinal detachment and significant post-operative pain. The patient was offered further surgical intervention for the retinal detachment as well as the possibility of a corneal transplant in the future, but the patient was not interested in further surgical intervention and ultimately underwent enucleation.

To determine if receiving a prescheduled appointment is associated with an increased likelihood of complying with follow-up eye care among individuals identified as at risk for glaucoma during community-based glaucoma screening in an urban underserved population. This study sampled 362 individuals aged ≥30 years without known glaucoma from low-income, predominantly black/Hispanic neighborhoods in New Haven, Connecticut presenting to one of twelve community-based glaucoma screening events from May 2010 to October 2012. A quasi-experimental design systematically assigned 63 individuals identified as at risk for glaucoma into either intervention or control group with a 1:2 ratio. Individuals in the control group (n = 41) received counseling on glaucoma and a recommendation for obtaining a follow-up appointment at the eye department of a local community health center, which offers affordable health services with income-adjusted fee discounts to uninsured, low-income patients. Those in the intervention group (n = 22) received the same counseling and a prescheduled appointment at the community health center. The overall rate of follow-up compliance within 3 months of screening was 30 % (41 % in the intervention group; 24 % in the control group). Multivariate logistic regression analysis adjusting for sex, age, ethnicity, health insurance status, car access, living situation, and smoking status found that follow-up compliance was significantly associated with intervention (adjusted odds ratio 4.8; 95 % confidence interval 1.1-20.9). Providing prescheduled appointments can improve follow-up compliance after community-based glaucoma screening. This finding may be potentially applicable to community-based health screening for other preventable diseases.

To identify barriers to follow-up eye care in children who failed a visual acuity screening conducted by their primary care provider.Children aged 3-14 years who failed a visual acuity screening were identified. A phone survey with the parent of every child was conducted 4 months after the screening. Family demographics, parental awareness of childhood eye diseases and eye care for children, and barriers to follow-up eye care were assessed.Of 971 children sampled, 199 (20.5%) failed a visual acuity screening. The survey was completed by the parents of 58 children (29.1%), of whom 27 (46.6%) presented for follow-up examination. The most common reason for failure to follow-up was parental unawareness of screening results (29.3%). Follow-up rates were higher in children with previous eye examinations than in those without (81% versus 17%; P = 0.005) and in children who waited2 months for a follow-up appointment than in those who had to wait longer (100% versus 63%; P = 0.024). Child's sex, ethnicity, and health insurance status, parent's marital, education and employment status, household income, and transportation access were not associated with statistically significant different follow-up rates.Parental unawareness of a failed visual acuity screening is an important barrier to obtaining follow-up. Strategies to improve follow-up rates after a failed visual acuity screening may include communicating the results clearly and consistently, providing education about the importance of timely follow-up, and offering logistic support for accessing eye appointments to families.

After 8 years of imprisonment, torture and maltreatment in Libya for allegedly infecting more than 400 children with HIV, purportedly in collusion with the CIA and Israeli secret service, 5 Bulgarian nurses and a Palestinian-born doctor were released on July 24. The 6 have repeatedly denied the charges. Libya has been internationally criticized for its disregard for scientific evidence, human rights and due process. As early as 2003, published molecular and epidemiological analyses provided compelling scientific evidence that exonerated the 6. Results of 2 international reports, filed respectively by the WHO and a scientific duo hired by the Libyan government itself — including Luc Montagnier, the co-discoverer of HIV — confirmed that the outbreak was nosocomial. Loath to acknowledge a home-grown AIDS epidemic that continues to spread due to poor hygiene practices and crumbling infrastructure, Libyan leaders have been accused in editorials in leading journals of using the foreign workers as scapegoats. The physician and nurses were ultimately released by Libyan leader Colonel Muammar el-Qaddafi on the basis of a 1984 accord between Bulgaria and Libya, which stipulates that citizens of one country convicted of crimes in the other can serve their sentences in their own nation. Cecilia Sarkozy, the wife of France's president, is said to have played a crucial diplomatic role in negotiating the release, thereby clinching a 3-year diplomatic process initiated by the European Union and taken forward by Tony Blair, the former British prime minister. After their release, the 6 went to Sofia, Bulgaria, where they were promptly pardoned by President Georgi Parvan. The release came with a price tag. The European Union promised medical support and US$426 million for the families of the infected children. The Union has also offered Libya trade agreements, scholarships and visas for travelling in Europe. France has expressed its intention to forge new economic ties with Libya, including helping to build superhighways and trains and develop new civil engineering, aerospace and defense projects. The seemingly cushy terms of this overdue release have sparked criticism. Susannah Sirkin, deputy director of the Boston-based Physicians for Human Rights has pointed out that “the lives of these nurses and medic were literally ransomed for $400 million.” Responding further to Libya's refusal to acknowledge concrete scientific and medical evidence during its trial of the health workers, Sirkin stated, “If this is not addressed, it will have a chilling effect on the willingness of people to enter the health professions and serve in areas where health care needs are great. And the health care in Libya will be no safer than it was when the children were infected.” — Tave van Zyl, CMAJ Figure. Palestinian-born Bulgarian doctor Ashraf al-Hazouz hugs his mother at a news conference in Sofia, Bulgaria. Photo by: Associated Press

HPV (human papillomavirus) is a highly contagious virus that is spread by skin-to-skin contact. It can infect the skin, the mouth, the rectum and the anus. It can also infect both male and female genital areas, including the skin on the penis or the vulva (area around the vagina), as well as the