Case report: Novel insights into hemorrhagic destruction of the brain, subependymal calcification, and cataracts disease.

Introduction: Pathogenic variants of the junctional adhesion molecule 3 (JAM3/JAM-C; OMIM#606871) is the cause of the rare recessive disorder called hemorrhagic destruction of the brain, subependymal calcification, and cataracts (HDBSCC, OMIM#613730) disease. A similar phenotype is universal, including congenital cataracts and brain hemorrhages with high mortality rate in the first few weeks of life and with a poor neurologic outcome in survivors. We aim to describe and enlighten novel phenotype and genotype of a new patient and review the literature regarding all reported patients worldwide. Case report: We report the case of a prenatal and postnatal phenotype of a new patient with a novel pathogenic loss-of-function variant in JAM3, who presented prenatally with cataracts and brain anomalies and postnatally with brain hemorrhages, failure to thrive (FTT), progressive microcephaly, recurrent posterior capsule opacities, and auditory neuropathy. Discussion: This study enlightens novel possible functions of JAM3 in the normal development of the brain, the ocular lenses, the auditory system, and possibly the gastrointestinal tract. This study is the first to report of cataracts evident in as early as 23 weeks of gestation and a rare phenomenon of recurrent posterior capsule opacities despite performing recurrent posterior capsulectomy and anterior vitrectomy. We suggest that auditory neuropathy, which is reported here for the first time, is part of the phenotype of HDBSCC, probably due to an endothelial microvasculature disruption of the peripheral eighth nerve or possibly due to impaired nerve conduction from the synapse to the brainstem. Conclusions: Prenatal cataracts, brain anomalies, FTT, and auditory neuropathy are part of the phenotype of the HDBSCC disease. We suggest including JAM3 in the gene list known to cause congenital cataracts, brain hemorrhages, and hearing loss. Further studies should address the auditory neuropathy and FTT phenomena in knockout mice models. We further suggest performing comprehensive ophthalmic, audiologic, and gastroenterologic evaluations for living patients worldwide to further confirm these novel phenomena in this rare entity.

[SLEEP MONITORING FOR PREDICTION OF MAJOR DEPRESSION RECURRENCE IN PATIENTS AT HIGH RISK - A PROSPECTIVE STUDY].

INTRODUCTION: Objective: To examine the feasibility of sleep monitoring using an innovative wearable technology, as a predictive tool for MDE (major depressive episode) recurrence in high risk patients.

Skin Eosinophil Counts in Bullous Pemphigoid as a Prognostic Factor for Disease Severity and Treatment Response.

Dermal infiltration of eosinophils and eosinophilic spongiosis are prominent features of bullous pemphigoid lesions. Although several observations support the pathogenic role of eosinophils in bullous pemphigoid, few studies have examined the impact of skin eosinophil counts on disease severity and treatment response. This retrospective study assessed the association between eosinophil counts in skin biopsy samples of 137 patients with bullous pemphigoid and their demographic characteristics, comorbidities, disease severity, and treatment response. There was no relationship between eosinophil count and age, sex, or disease severity at disease onset. There was a positive relationship between eosinophil counts and neurological comorbidity and a negative relationship between eosinophil counts and treatment response. At all follow-up points patients with no tissue eosinophils had a better response to treatment than patients with any tissue eosinophil count. In conclusion, skin eosinophil counts in patients with bullous pemphigoid are not correlated with disease severity at onset, but can serve as a negative prognostic marker for treatment response.

Long term ophthalmic complications of distal arthrogryposis type 5D.

BACKGROUND: Distal Arthrogryposis type 5D (DA5D) is a rare genetic disease, expressed phenotypically by skeletal and ocular abnormalities. MATERIALS AND METHODS: Two sisters, ages 42 and 46 years old, were ascertained, both diagnosed with arthrogryposis and unusual ophthalmic late expressions of the disease. They were examined and followed up by both ophthalmologists and medical geneticists. Molecular analysis was performed and population screening followed among healthy individuals of the same ethnic background who reside in the same village. RESULTS: The two sisters expressed myogenic ptosis with poor levator palpebrae function, limitation in up gaze, lagophthalmos, refractive errors, corneal scarring and vascularization along with severe distal arthrogryposis. The newly reported features were: significant lower lid retraction, causing inferior scleral show. Sanger sequencing of the coding regions of ECEL1 gene revealed a homozygous deletion of 46 bps. The carrier frequency is 1:24 (4.2% carriers) in the probands' village. CONCLUSIONS: We diagnosed two patients with DA5D carrying a homozygous pathogenic genetic variant previously reported only once. We report the late ophthalmologic manifestations of this rare disorder and emphasize the importance to recognize possible long-term ophthalmic complications. Measures are needed to diagnose this rare disorder at a younger age and to address ophthalmic and orthopedic complications that might be prevented. We revealed the causative genetic variant and a carrier frequency of 1:24 for DA5D, in the probands' village, thus enabling accurate genetic counselling and justifying genetic testing to the residents of this village as a diagnostic and preventive measure.

Congenital Hypotonia: Cracking a SAGA of consanguineous kindred harboring four genetic variants.

BACKGROUND: We aimed to determine the molecular and biochemical basis of an extended highly consanguineous family with multiple children presenting severe congenital hypotonia. METHODS: Clinical investigations, homozygosity mapping, linkage analyses and whole exome sequencing, were performed. mRNA and protein levels were determined. Population screening was followed. RESULTS: We have identified a novel nonsense variant in NGLY1 in two affected siblings, and compound heterozygosity for three novel RYR1 variants in two affected sisters from another nuclear family within the broad pedigree. Population screening revealed a high prevalence of carriers for both diseases. The genetic variants were proven to be pathogenic, as demonstrated by western blot analyses. CONCLUSIONS: Revealing the genetic diagnosis enabled us to provide credible genetic counselling and pre-natal diagnosis to the extended family and genetic screening for this high-risk population. Whole exome/genome sequencing should be the first tier tool for accurate determination of the genetic basis of congenital hypotonia. Two different genetic disorders within a large consanguineous pedigree should be always considered.

Solid organ transplantation worsens the prognosis of patients with cutaneous squamous cell carcinoma of the head and neck region-Comparison between solid organ transplant recipients and immunocompetent patients.

BACKGROUND: Cutaneous squamous cell carcinoma of the head and neck (CSCC-HN) appears to behave more aggressively in immunosuppressed patients. We aimed to investigate this hypothesis by comparing solid organ transplant recipients (SOTR) with CSCC-HN to immunocompetent patients. METHODS: A retrospective comparative study was conducted for SOTR and immunocompetent patients who were treated for CSCC-HN. RESULTS: A total of 177 SOTR and 157 immunocompetent patients with CSCC-HN were included. Lymph node metastases were more common in the SOTR group (9% vs 3%), and distant metastases occurred only in SOTR (3% of patients). SOTR had a higher rate of recurrences (19% vs 10%), which were mostly regional (7%) and distant (3%). The 2-year disease-specific survival of SOTR was lower (93% vs 100%). CONCLUSIONS: SOTR with CSCC-HN has significantly worse outcomes compared to immunocompetent patients. Solid-organ transplantation should be regarded as a negative prognostic factor in patients with CSCC-HN.

Development of a machine learning algorithm for early detection of opioid use disorder.

BACKGROUND: Opioid use disorder (OUD) affects an estimated 16 million people worldwide. The diagnosis of OUD is commonly delayed or missed altogether. We aimed to test the utility of machine learning in creating a prediction model and algorithm for early diagnosis of OUD. SUBJECTS AND METHODS: We analyzed data gathered in a commercial claim database from January 1, 2006, to December 31, 2018 of 10 million medical insurance claims from 550 000 patient records. We compiled 436 predictor candidates, divided to six feature groups - demographics, chronic conditions, diagnosis and procedures features, medication features, medical costs, and episode counts. We employed the Word2Vec algorithm and the Gradient Boosting trees algorithm for the analysis. RESULTS: The c-statistic for the model was 0.959, with a sensitivity of 0.85 and specificity of 0.882. Positive Predictive Value (PPV) was 0.362 and Negative Predictive Value (NPV) was 0.998. Significant differences between positive OUD- and negative OUD- controls were in the mean annual amount of opioid use days, number of overlaps in opioid prescriptions per year, mean annual opioid prescriptions, and annual benzodiazepine and muscle relaxant prescriptions. Notable differences were the count of intervertebral disc disorder-related complaints per year, post laminectomy syndrome diagnosed per year, and pain disorders diagnosis per year. Significant differences were also found in the episodes and costs categories. CONCLUSIONS: The new algorithm offers a mean 14.4 months reduction in time to diagnosis of OUD, at potential saving in further morbidity, medical cost, addictions and mortality.

Machine learning algorithm for early detection of end-stage renal disease.

BACKGROUND: End stage renal disease (ESRD) describes the most severe stage of chronic kidney disease (CKD), when patients need dialysis or renal transplant. There is often a delay in recognizing, diagnosing, and treating the various etiologies of CKD. The objective of the present study was to employ machine learning algorithms to develop a prediction model for progression to ESRD based on a large-scale multidimensional database. METHODS: This study analyzed 10,000,000 medical insurance claims from 550,000 patient records using a commercial health insurance database. Inclusion criteria were patients over the age of 18 diagnosed with CKD Stages 1-4. We compiled 240 predictor candidates, divided into six feature groups: demographics, chronic conditions, diagnosis and procedure features, medication features, medical costs, and episode counts. We used a feature embedding method based on implementation of the Word2Vec algorithm to further capture temporal information for the three main components of the data: diagnosis, procedures, and medications. For the analysis, we used the gradient boosting tree algorithm (XGBoost implementation). RESULTS: The C-statistic for the model was 0.93 [(0.916-0.943) 95% confidence interval], with a sensitivity of 0.715 and specificity of 0.958. Positive Predictive Value (PPV) was 0.517, and Negative Predictive Value (NPV) was 0.981. For the top 1 percentile of patients identified by our model, the PPV was 1.0. In addition, for the top 5 percentile of patients identified by our model, the PPV was 0.71. All the results above were tested on the test data only, and the threshold used to obtain these results was 0.1. Notable features contributing to the model were chronic heart and ischemic heart disease as a comorbidity, patient age, and number of hypertensive crisis events. CONCLUSIONS: When a patient is approaching the threshold of ESRD risk, a warning message can be sent electronically to the physician, who will initiate a referral for a nephrology consultation to ensure an investigation to hasten the establishment of a diagnosis and initiate management and therapy when appropriate.

Randomized Controlled Phase 2a Study of RPh201 in Previous Nonarteritic Anterior Ischemic Optic Neuropathy.

BACKGROUND: No proven treatment exists for nonarteritic anterior ischemic optic neuropathy (NAION), either in the acute or late phase. OBJECTIVE: To assess safety and changes in visual function and structure after RPh201/placebo treatment in participants with previous NAION. DESIGN AND SETTING: Phase 2a, single-site, prospective, randomized, placebo-controlled, double-masked trial (registration NCT02045212). MAIN OUTCOMES MEASURES: Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA), visual fields, retinal nerve fiber layer, and visual evoked potential at weeks 13, 26, and after a 13-week wash-out ("off-drug") period; and safety. STUDY POPULATION: Twenty-two participants aged 18 years or older with previous NAION. INTERVENTION(S): RPh201 (20 mg) or placebo (cottonseed oil vehicle) administered subcutaneously twice weekly at the study site. RESULTS: Thirteen men and 9 women were randomized, of which 20 completed all visits. The mean (±SD) age was 61.0 ± 7.6 years. In a post hoc analysis, after 26 weeks of treatment, BCVA improved by ≥15 letters in 4/11 (36.4%) eyes with RPh201, compared to 1/8 (12.5%) eyes with placebo (P = 0.24). Overall, 7/11 (63.6%) of participants on RPh201 showed some improvement in BCVA, compared with 3/8 (37.5%) on placebo (P = 0.26). Improvement in BCVA from a calculated baseline was 14.8 ± 15.8 letters for RPh201 and 6.6 ± 15.3 for placebo (P = 0.27). Of the 154 adverse effects (AEs), 52 were considered related to the study procedures/treatment. Across the study and 1,017 injections, the most frequently reported AE was injection site pain (23 events in 5 participants). There were no clinically significant changes in vital signs or laboratory values. CONCLUSIONS: This Phase 2a was designed to assess safety, feasibility, and explore potential efficacy signals in treating previous NAION with RPh201. No safety concerns were raised. The results support a larger trial in patients with previous NAION.

[EXTRINSIC AND INTRINSIC FACTORS FOR FALLS THAT CAUSED HIP FRACTURE].

INTRODUCTION: Among the reasons described as possibly causing falls in older and elderly people are extrinsic factors such as bumping into objects, slipping on a wet floor, etc., and intrinsic factors - those that occur suddenly without warning. OBJECTIVES: To investigate the connection between the reasons for falls, extrinsic or intrinsic and different medical and nonmedical factors. METHODS: The survey included 82 people, 53 women and 29 men, who fell and broke their hip, underwent surgery, and were treated at the Rehabilitation Department. Data showed that 39 people fell due to extrinsic factors and 43 due to intrinsic reasons. We examined the correlation with several factors, both medical and non-medical, that may have influenced the scenario of each group. RESULTS: Falls due to extrinsic reasons took place at all hours of the day and night, mainly in people who were alone and who wore shoes or sandals at the time of the fall and who either suffered from slight or no disturbances in attention and concentration. Falls due to intrinsic reasons occurred mainly during rest or sleep hours, in people who walked barefoot or with socks or slippers and who suffered moderate or severe disturbances in attention and concentration. CONCLUSIONS: Although the differences in the extrinsic vs. intrinsic reasons for falls that led to broken hips were fairly clear, it would be difficult to recommend new tools for prevention of this phenomenon. Trying to predict an infrequent future event such as a traumatic fall is inherently difficult.

Sequence variation in PPP1R13L results in a novel form of cardio-cutaneous syndrome.

Dilated cardiomyopathy (DCM) is a life-threatening disorder whose genetic basis is heterogeneous and mostly unknown. Five Arab Christian infants, aged 4-30 months from four families, were diagnosed with DCM associated with mild skin, teeth, and hair abnormalities. All passed away before age 3. A homozygous sequence variation creating a premature stop codon at PPP1R13L encoding the iASPP protein was identified in three infants and in the mother of the other two. Patients' fibroblasts and PPP1R13L-knocked down human fibroblasts presented higher expression levels of pro-inflammatory cytokine genes in response to lipopolysaccharide, as well as Ppp1r13l-knocked down murine cardiomyocytes and hearts of Ppp1r13l-deficient mice. The hypersensitivity to lipopolysaccharide was NF-κB-dependent, and its inducible binding activity to promoters of pro-inflammatory cytokine genes was elevated in patients' fibroblasts. RNA sequencing of Ppp1r13l-knocked down murine cardiomyocytes and of hearts derived from different stages of DCM development in Ppp1r13l-deficient mice revealed the crucial role of iASPP in dampening cardiac inflammatory response. Our results determined PPP1R13L as the gene underlying a novel autosomal-recessive cardio-cutaneous syndrome in humans and strongly suggest that the fatal DCM during infancy is a consequence of failure to regulate transcriptional pathways necessary for tuning cardiac threshold response to common inflammatory stressors.

Infants under two months of age with urinary tract infections are showing increasing resistance to empirical and oral antibiotics.

AIM: Data on antimicrobial resistance in uropathogens in infants up to the age of three months are limited. This study characterised resistance patterns in Gram-negative uropathogens in infants up to the age of two months. METHODS: Previously healthy young infants with urinary tract infections (UTIs) were studied retrospectively. Antimicrobial susceptibility was evaluated. Multidrug resistance (MDR) was defined as resistance to at least three antibiotic classes. Clinical, laboratory and outcome data were compared between infants with UTIs caused by bacteria sensitive and resistant to empirical and to oral therapy. RESULTS: We evaluated 306 UTI episodes with 314 pathogens. The following resistance rates were observed: ampicillin 73.7%, cefazoline 22.1%, ampicillin/clavulanate 21.8%, cefuroxime 7.8%, gentamicin 7%; MDR 11.8%; resistant to empirical treatment 7.3% and resistant to available oral antibiotics 8.6%. Our study showed that pathogens resistant to empirical and oral therapy were more frequently isolated in non-Jewish (Arab) infants and in those of ≥30 days of age. Resistance to empirical treatment and oral antibiotics also resulted in longer mean hospital stays. CONCLUSION: Resistance to antibiotics challenges empirical therapy and compromises oral treatment options in young infants with UTIs. Antimicrobial resistance patterns should be monitored in infants to determine appropriate empirical antibiotic therapy protocols.

VALIDATION OF AN ALGORITHM FOR NONMETALLIC INTRAOCULAR FOREIGN BODIES' COMPOSITION IDENTIFICATION BASED ON COMPUTED TOMOGRAPHY AND MAGNETIC RESONANCE IMAGING.

PURPOSE: To validate and evaluate the accuracy of an algorithm for the identification of nonmetallic intraocular foreign body composition based on computed tomography and magnetic resonance imaging. METHODS: An algorithm for the identification of 10 nonmetallic materials based on computed tomography and magnetic resonance imaging has been previously determined in an ex vivo porcine model. Materials were classified into 4 groups (plastic, glass, stone, and wood). The algorithm was tested by 40 ophthalmologists, which completed a questionnaire including 10 sets of computed tomography and magnetic resonance images of eyes with intraocular foreign bodies and were asked to use the algorithm to identify their compositions. Rates of exact material identification and group identification were measured. RESULTS: Exact material identification was achieved in 42.75% of the cases, and correct group identification in 65%. Using the algorithm, 6 of the materials were exactly identified by over 50% of the participants, and 7 were correctly classified according to their groups by over 75% of the materials. DISCUSSION: The algorithm was validated and was found to enable correct identification of nonmetallic intraocular foreign body composition in the majority of cases. This is the first study to report and validate a clinical tool allowing intraocular foreign body composition based on their appearance in computed tomography and magnetic resonance imaging, which was previously impossible.

Clinical profile of fallers with femoral neck fractures.

OBJECTIVE: To describe the most common characteristics of elderly people who fell and fractured their femoral neck and who were admitted to our rehabilitation setting after surgery by an orthopedic surgeon. SETTING: A rehabilitation department in a general regional hospital. PARTICIPANTS: A cohort of 100 patients, 37 men and 63 women, hospitalized for rehabilitation after surgery for a fracture in the femoral neck. METHODS: All the patients were interviewed by a physician from the rehabilitation department about the circumstances of their fall injuries, examined by an ophthalmologist for ocular problems, and evaluated by an occupational therapist for cognitive function. Data about background diseases were retrieved from the patients' medical records. MAIN OUTCOME MEASUREMENTS: Age of the patients, place and time of the fall, the circumstances of the fall event, the footwear used at the time of the fall, ophthalmic problems, cognitive disorders, eyeglasses use, walking aids use, medication used that may affect the central nervous system, and the presence of diseases that may influence patients' equilibrium. RESULTS: The mean age of the patients was 78 years, with a mean weight of 69 kg. Seventy-eight percent had 1-5 diseases that could influence their balance during weight bearing; 67% had an ophthalmic disease. For 70% of the patients, the cause of the fall appeared to be intrinsic (personal). Seventy-two percent wore socks or slippers, or were barefoot at the time of the fall. Sixty-four percent of the patients who used a walking aid did not use it during the fall event. Seventy-one percent of falls occurred indoors and 29% outdoors. Fifty-five percent of the patients were with another person when they fell. Fifty-one percent were taking tranquilizers or medications for sleep disorders. Sixty-eight percent fell during the daylight hours, between 6 AM and 6 PM. Of the patients who wore eyeglasses, 77.6% were not wearing them when they fell. Seventy percent had a short-term memory disorder, 57% had a concentration disorder, and 49% had an orientation disorder. CONCLUSIONS: Characteristics common to patients who fell and fractured their femoral neck included age older than 78 years, cognitive impairment, nonuse of eyeglasses that were prescribed, and inappropriate footwear.

A novel XPD mutation in a compound heterozygote; the mutation in the second allele is present in three homozygous patients with mild sun sensitivity.

The XPD protein plays a pivotal role in basal transcription and in nucleotide excision repair (NER) as one of the ten known components of the transcription factor TFIIH. Mutations in XPD can result in the DNA repair-deficient diseases xeroderma pigmentosum (XP), trichothiodystrophy (TTD), cerebro-oculo-facial-skeletal syndrome, and in combined phenotypes such as XP/Cockayne syndrome and XP/TTD. We describe here an 18-year-old individual with mild sun sensitivity, no neurological abnormalities and no tumors, who carries a p.R683Q mutation in one allele, and the novel p.R616Q mutation in the other allele of the XPD gene. We also describe four patients from one family, homozygous for the identical p.R683Q mutation in XPD, who exhibit mild skin pigmentation and loss of tendon reflexes. Three homozygous patients presented with late-onset skin tumors, and two with features of premature aging and moderate cognitive decline. Cells from the compound heterozygous individual and from one of the patients homozygous for p.R683Q exhibited similar responses to UV irradiation: reduced viability and defective overall removal of UV-induced cyclobutane pyrimidine dimers, implying deficient global genomic NER. Cells from the compound heterozygous subject also failed to recover RNA synthesis after UV, indicating defective transcription-coupled NER. Mutations affecting codon 616 in XPD generally result in functionally null proteins; we hypothesize that the phenotype of the heterozygous patient results solely from expression of the p.R683Q allele. This study illustrates the importance of detailed follow up with sun sensitive individuals, to ensure appropriate prophylaxis and to understand the mechanistic basis of the implicated hereditary disease.

Falls in stroke patients: risk factors and risk management.

BACKGROUND: Falls are common events among hospital inpatients and constitute a major health problem in the rehabilitation setting. Many risk factors for falls have been identified for stroke patients, such as muscle weakness, medication side effects, hypoglycemia, hypotension, etc. OBJECTIVES: To assess the risk factors for falls among patients hospitalized for rehabilitation following acute stroke. METHODS: In a retrospective study of 56 falls over a period of 5 years in 41 stroke patients hospitalized for rehabilitation we surveyed the nurses' safety risk assessment of the fall. Thirty patients fell once, 9 patients twice and 2 patients four times. The data were obtained from the medical and nursing records. Safety precautions were taken by the nurses for the entire group of patients. RESULTS: Most of the falls occurred among male patients who had reduced muscular tone (70%), paralysis (54%) and/ or hypoesthesia in the involved side of the body. Patients who suffered from hemiplegia fell more often than those with hemiparesis (Wilcoxon rank sum test, P = 0.04, one-sided). Forty-eight percent of the falls occurred during the first month after the last stroke, 70% during the morning or the afternoon, and 62% occurred close to the patient's bed. In 89% of falls the patients used hypoglycemic, antihypertensive, tranquilizing or neuroleptic drugs. Communication disorders (29%), hemianopia or blindness (21%) and visuospatial agnosia (18%) were incremental risk factors for falls. Fifty percent of the falls were caused by either an intrinsic or extrinsic mechanism. CONCLUSIONS: These data suggest that the group of stroke patients at risk for falls in a rehabilitation department can be identified by a variety of impairment and functional assessments. The information may be potentially useful for designing interventions directed at reducing fall frequency among stroke survivors.

Achieving quality in a government hospital: departmental responsibility.

Quality improvement in health care organizations requires structural reorganization and system reform and the development of an appropriate organizational "culture." In 2007, the Division of Quality and Excellence in Civil Service in Israel developed a concept to improve quality management in governmental institutions throughout the country. To put this strategy into practice, Western Galilee Hospital, a governmental hospital, in northern Israel, developed a plan to advance the quality management system where each department and unit is autonomously responsible for its own quality and excellence. Since the hospital has been certificated by ISO 9001 for more than 10 years (the only hospital in Israel to have this certificate), the main challenge now is to improve the quality and excellence system in every department. The aim of this article is to describe the implementation of a comprehensive program designed to raise the ability of managers and workers in Western Galilee Hospital in addressing all of the government's requirements for quality and excellence in service in Israel.

Eruptive acral lentigines--a new paraneoplastic sign?

Cutaneous signs may be the first indications of an internal disease. Any definitive sign of a neoplastic disease is of special importance since early diagnosis and early treatment may make a telling difference in improving prognosis. Presented is a 68-year-old patient with advanced stage melanoma that was associated with the appearance of multiple acral lentigines. The exact time-course of onset of the lentigines in relation to the formation of the melanoma could not be established. However, from the information we could take out of our patient, it is clear that the lentigines had appeared either shortly before or after the appearance of the melanoma. In conclusion we suggest that the present case represents a new paraneoplastic sign.

The spectrum of iatrogenic intraocular injuries caused by inadvertent cannula release during anterior segment surgery.

OBJECTIVE: To evaluate the causes of inadvertent intraocular injuries resulting from the use of cannulas during anterior segment surgery. Method Retrospective review of all cases with inadvertent release of irrigation and viscoelastic cannulas during anterior segment surgery in 15 years. RESULTS: Inadvertent release of cannulas occurred in 9 of 10 230 cases of anterior segment surgery during a 15-year period. The incidence of cannula release was 0.88 per 1000 procedures per year. Twenty percent of the surgeons who performed anterior segment surgery in this period were involved in this unfortunate event. Six cases occurred during cataract extraction and 3 during penetrating keratoplasty or replacement of corneal graft. The latter 3 cases included posterior capsule rupture and vitreous loss. Macular scar in 2 (22%) of the 9 cases was associated with poor visual outcome of counting fingers at 2.1 to 3.0 m (P = .03). In all other surgeries, the cannula caused iris or anterior chamber angle injury without consequences. CONCLUSIONS: Inadvertent release of cannulas during anterior segment surgery is a rare, memorable, and unfortunate event. The severity of the injury may be related to the type of the surgical wound. In most cases, visual outcome is not compromised unless the cannula causes retinal disruption.