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Background: The BenchMarket Medical (BMM) Vertebral Compression Fracture (VCF) Registry, now known as Talosix, is a collaborative effort between Talosix (the authorized registry vendor), Noridian Healthcare Solutions, and clinicians to gather outcomes evidence for cement augmentation treatments in patients with acute painful osteoporotic VCFs. The VCF Registry was designed to provide outcomes evidence to inform the Medicare payer’s “coverage with evidence development” decision to authorize reimbursement for cement augmentation treatments. Objectives: The purpose of this article was to present a pathway for appropriate use of vertebral augmentation based on the findings of the VCF Registry. Study Design: Prospective observational data, including patient characteristics, diagnosis, process of care, and patient-reported outcomes (PROs) for pain and function, were collected from patients undergoing cement augmentation treatment. The PROs were collected at baseline, 1, 3, and 6 months following the procedure. Setting: The VCF Registry is a national ongoing registry with no specified end time or designated sample size. Methods: Primary outcomes were pain improvement measured using the Numeric Rating Scale and function improvement, measured using the Roland Morris Disability Questionnaire (RMDQ). Secondary outcomes included cement leakage, new neurologic deficits, adverse events, readmissions, and death. Results: The VCF Registry delivered outcomes data to support Noridian’s “coverage with evidence development” decision. A total of 732 patients were included in this study. Registry outcomes confirmed postmarket evidence of highly significant pain relief with mean pain score improvement of 6.5/10 points at 6 months. Function also improved significantly with mean RMDQ score change of 11.4/24 points 6 months after surgery. Results also showed the safety and reliability of cement augmentation. Limitations: The nature of the registry data is that it contains nonrandomized, nonplacebo controlled data and should not be perceived as such. The real-world setting and the large number of patients within the dataset should increase the external validity of the findings. Conclusions: Cement augmentation treatments of patients with acute painful VCFs reliably results in highly significant benefits of pain decrease and functional improvement for this Medicare population. Key words: Vertebral compression fractures, osteoporosis, kyphoplasty, back pain, registry

Back pain is the second most common reason for primary-care physician visits after the common cold. New understanding of the spine pathophysiology and biomechanics led to the development of novel injectable biomaterials to treat those pain generators. Although not all biomaterials are currently ready for common use, there is significant interest by the medical community to invest time, resources, and energy to optimize these injectables. This review introduces basic concepts and advancements in the field of bioinjectables tailored for the vertebral body. Also, we highlight advances in injectable biomaterials which were presented at the Groupe de Recherche Interdisciplinaire sur les Biomatériaux Ostéoarticulaires Injectables (GRIBOI) (Interdisciplinary Research Society for Injectable Osteoarticular Biomaterials) meeting in March 2018 in Los Angeles, CA. Indeed, multidisciplinary translational research and international meetings such as GRIBOI bring together scientists and clinicians with different backgrounds/expertise to discuss injectable biomaterials innovations tailored for the interventional pain management field.

Intrathecal drug delivery has expanded since the inception of this technology in the 1980s and is utilized for a number of different conditions including pain control and management of spasticity. The use of intrathecal pumps is less common than most other techniques for interventional pain management but is essential in such conditions as refractory pain, cancer pain, multifocal pain, severe spasticity, and in patients who are not candidates for surgical correction of their underlying condition. Intrathecal drug delivery is usually considered when analgesics or antispasmodics administered via the oral, transdermal, or intravenous routes are ineffective or are associated with unacceptable side effects. The intrathecal delivery of medications bypasses the blood–brain barrier, which produces much higher concentrations of medication within the cerebrospinal fluid. This higher concentration can serve to dramatically reduce the effective dose of the medication and can be associated with higher rates of pain and spasm reduction compared to other routes of medication delivery. Although intrathecal drug delivery has been shown to be effective and cost-effective this less utilized pain management tool is less well understood regarding its implantation and management than other technologies. This chapter will serve to highlight the proper clinical use and appropriate management of intrathecal pumps for the management of spasticity and pain.

The BenchMarket Medical (BMM) Vertebral Compression Fracture (VCF) Registry, now known as Talosix, is a collaborative effort between Talosix (the authorized registry vendor), Noridian Healthcare Solutions, and clinicians to gather outcomes evidence for cement augmentation treatments in patients with acute painful osteoporotic VCFs. The VCF Registry was designed to provide outcomes evidence to inform the Medicare payer's "coverage with evidence development" decision to authorize reimbursement for cement augmentation treatments.The purpose of this article was to present a pathway for appropriate use of vertebral augmentation based on the findings of the VCF Registry.Prospective observational data, including patient characteristics, diagnosis, process of care, and patient-reported outcomes (PROs) for pain and function, were collected from patients undergoing cement augmentation treatment. The PROs were collected at baseline, 1, 3, and 6 months following the procedure.The VCF Registry is a national ongoing registry with no specified end time or designated sample size.Primary outcomes were pain improvement measured using the Numeric Rating Scale and function improvement, measured using the Roland Morris Disability Questionnaire (RMDQ). Secondary outcomes included cement leakage, new neurologic deficits, adverse events, readmissions, and death.The VCF Registry delivered outcomes data to support Noridian's "coverage with evidence development" decision. A total of 732 patients were included in this study. Registry outcomes confirmed postmarket evidence of highly significant pain relief with mean pain score improvement of 6.5/10 points at 6 months. Function also improved significantly with mean RMDQ score change of 11.4/24 points 6 months after surgery. Results also showed the safety and reliability of cement augmentation.The nature of the registry data is that it contains nonrandomized, nonplacebo controlled data and should not be perceived as such. The real-world setting and the large number of patients within the dataset should increase the external validity of the findings.Cement augmentation treatments of patients with acute painful VCFs reliably results in highly significant benefits of pain decrease and functional improvement for this Medicare population.Vertebral compression fractures, osteoporosis, kyphoplasty, back pain, registry.

Degenerative disc disease is a ubiquitously common process that occurs with normal aging but can give rise to back pain that can range from mild to severe. The pain and disability caused by DDD account for a very large number of doctor visits and are the most common causes of disability worldwide. The treatment for DDD has largely been supportive but new biomaterials including fibrin adhesives, platelet-rich plasma, bone morphogenic protein, transforming growth factor, alpha-2-macroglobulin, and autologous and allogeneic mesenchymal stem cells have been used with varying degrees of success. Some of the recent biologic injectables have shown significant promise in relieving pain and restoring function in patients with painful DDD, and there have also been some signs of anatomic regeneration on cross-sectional imaging evaluation as well. It appears that some of the existing biomaterials will be safe and will be very effective in treating patients with painful DDD.

Developing simpler, more accessible, and more affordable methods for the determination of the boiling point of microscale amounts of liquid may lead to increased utilization in research and teaching laboratories as an analytical technique. Our efforts toward that goal have revealed that digital hot plates can be used as the heat source. One option is to simply use a test tube and a digital thermometer, requiring 300 μL of liquid that accurately determines boiling points that range from 35 to 150 °C. An alternative method, requiring as little as 30 μL of liquid, utilizes a modified aluminum block and a temperature control probe coupled to the digital hot plate that results in the accurate determination of boiling points that range from 35 to 205 °C. Both modifications to the Siwoloboff–Wiegand method provide consistent, reliable, and accurate boiling points for a variety of liquids with a wide range of boiling points.

Purpose To determine the incidence of positive corneoscleral donor rim fungal cultures after keratoplasty and to report clinical outcomes of grafts with culture-positive donor rims. Design Retrospective cohort study. Participants Consecutive donor corneas and keratoplasty recipients at a single tertiary referral center over 20 years. Methods Patient charts were reviewed to determine the incidence of positive donor rim fungal cultures and clinical outcomes of all grafts using contaminated tissue. Main Outcome Measures The primary outcome measures were positive donor rim fungal culture results and the development of postkeratoplasty fungal infection using corresponding corneal tissue. The secondary outcome measure was the impact of postoperative prophylaxis on donor tissue-associated infections. Results A total of 3414 keratoplasty cases were included in the statistical analysis. Seventy-one cases (2.1%) were associated with a fungal culture-positive donor rim. Candida species were cultured in 40 cases (56.3%). There was a higher incidence of positive rim cultures over the last 5 years of the analytic period compared with the first 15 years ( P = 0.018). Fungal keratitis developed in 4 cases (5.6%), and all patients required further surgical intervention to achieve cure. There were no cases of fungal endophthalmitis. Empiric antimycotic prophylaxis initiated at the time of positive culture result reduced the incidence of keratitis from 15.8% in untreated cases to 1.9% in treated cases ( P = 0.056). Conclusions Positive donor rim fungal cultures are uncommon, but carry an unacceptably high risk of postoperative fungal infection. This risk may be reduced with prophylactic antimycotic therapy when culture-positive donor rims are identified.

Purpose To compare the incidence of visually significant postoperative cystoid macular edema (CME) in pseudophakic eyes after Descemet membrane endothelial keratoplasty (DMEK) performed after recent versus remote cataract surgery. Methods A retrospective chart review was performed of all consecutive eyes that underwent DMEK without concurrent cataract surgery at the University of Iowa between October 2012 and December 2014. The DMEK procedures were classified as staged if performed between 2 weeks and 6 months after cataract surgery and solitary if performed more than 6 months after cataract surgery. Possible confounders, including a history of diabetes in the recipient, were tracked. Macular optical coherence tomography was performed to detect CME 1 month after DMEK if the best-corrected visual acuity was ≤20/30 with a clear cornea with no other reason for visual compromise. Results A total of 173 eyes from 140 patients were included in the statistical analysis. Staged DMEK was performed in 88 eyes (50.8%) and solitary DMEK in 85 eyes (49.2%). The incidence of CME was 8.0% (7 of 88 eyes) in the staged DMEK group and 7.1% (6 of 85 eyes) in the solitary DMEK group (P = 0.823). The incidence of CME did not differ significantly between the staged and solitary DMEK groups regardless of the recipient diabetic status. All cases of CME resolved within 6 months on topical therapy. Conclusions The incidence of postoperative CME after DMEK is similar in the setting of recent or remote cataract surgery.

The purpose of this study was to devise a strategy for the derivation of corneal endothelial cells (CEnCs) from adult fibroblast-derived induced pluripotent stem cells (iPSCs). IPSCs were generated from an adult human with normal ocular history via expression of OCT4, SOX2, KLF4 and c-MYC. Neural crest cells (NCCs) were differentiated from iPSCs via addition of CHIR99021 and SB4315542. NCCs were driven toward a CEnC fate via addition of B27, PDGF-BB and DKK-2 to CEnC media. Differentiation of NCCs and CEnCs was evaluated via rt-PCR, morphological and immunocytochemical analysis. At 17 days post-NCC induction, there were notable changes in cell morphology and upregulation of the neural crest lineage transcripts PAX3, SOX9, TFAP2A, SOX10 and p75NTR and the proteins p75/NGFR and SOX10. Exposure of NCCs to B27, PDGF-BB and DKK-2 induced a shift in morphology from a spindle-shaped neural phenotype to a tightly-packed hexagonal appearance and increased expression of the transcripts ATP1A1, COL8A1, COL8A2, AQP1 and CDH2 and the proteins ZO-1, N-Cad, AQP-1 and Na+/K+ATPase. Replacement of NCC media with CEnC media on day 3, 5 or 8 reduced the differentiation time needed to yield CEnCs. IPSC-derived CEnCs could be used for evaluation of cornea endothelial disease pathophysiology and for testing of novel therapeutics., Summary: This study demonstrates differentiation of adult dermal fibroblast-derived iPSCs into neural crest and corneal endothelial-like cells, which could be a valuable tool for investigating the mechanisms of cornea endothelial disease.

To evaluate the outcome of the Boston type 1 keratoprosthesis (KPro-1) in eyes with iridocorneal endothelial syndromes and failed keratoplasties.A retrospective review was performed of every eye with a history of iridocorneal endothelial syndrome and a failed corneal transplant that was treated with a KPro-1 at a tertiary eye care center between January 1, 2008, and July 1, 2014. The main outcome measures were visual outcome, prosthesis retention, and postoperative complications.Four eyes met the inclusion criteria. Two eyes had essential iris atrophy and 2 eyes had Chandler syndrome. All 4 eyes had failed corneal transplants and successful glaucoma drainage devices. The mean patient age at the time of KPro-1 surgery was 68.3 years (range, 60-80 years). The mean postoperative follow-up duration was 47 months (range, 27-69 months). Preoperatively, the best-corrected visual acuity (BCVA) was worse than 20/200 in all 4 eyes, including 2 eyes that had hand motions vision. After KPro-1, all 4 eyes initially obtained a BCVA of ≥20/70. At the most recent examination, the BCVA was still ≥20/100 in 3 eyes. The KPro-1 device was retained in all 4 eyes. Postoperative complications included glaucoma progression (1 eye), a retroprosthetic membrane (1 eye), and sterile vitritis (1 eye).The Boston KPro-1 may offer a better prognosis than repeat traditional keratoplasty in reestablishing corneal clarity in eyes with iridocorneal endothelial syndromes. Despite anatomic success, visual rehabilitation may be compromised by preexisting glaucomatous optic neuropathy and its postoperative progression.

The purpose of this study was to evaluate the outcomes of the Boston type 1 keratoprosthesis (Kpro-1) in eyes with failed keratoplasty. A retrospective review was performed of every patient treated with a Kpro-1 at a tertiary eye care center between January 1, 2008 and July 1, 2013. Eyes with a failed keratoplasty originally performed for corneal edema, trauma, or keratoconus were included in the statistical analysis. The main outcome measures were visual outcome, prosthesis retention, and postoperative complications. Twenty-four eyes met the inclusion criteria, including 13 eyes with corneal edema, 8 eyes with trauma, and 3 eyes with keratoconus. After a mean follow-up period of 28.9 months (range 7-63 months), the median best corrected visual acuity (BCVA) was 20/125. The BCVA was ≥ 20/40 in 4 (16.7 %) eyes, ≥ 20/70 in 9 (37.5 %) eyes, and ≥ 20/200 in 14 (58.3 %) eyes. Overall, the postoperative BCVA improved in 17 (70.9 %) eyes, was unchanged in 3 (12.5 %) eyes, and was worse in 4 (16.7 %) eyes. The initial Kpro-1 was retained in 22 (91.7 %) eyes, and was successfully repeated in the other 2 eyes. One or more serious prosthesis- or sight-threatening complications occurred in 8 (33.3 %) eyes. These included 1 case of wound dehiscence leading to prosthesis extrusion, 1 case of fungal keratitis leading to prosthesis extrusion, 4 cases of endophthalmitis, and 5 retinal detachments. The Boston Kpro-1 is associated with an excellent prognosis for prosthesis retention and satisfactory visual improvement in eyes with previous failed keratoplasty.

Purpose To compare corneal graft survival using tissue from diabetic and nondiabetic donors in patients undergoing initial Descemet stripping automated endothelial keratoplasty (DSAEK) or penetrating keratoplasty (PKP). Methods A retrospective chart review of pseudophakic eyes that underwent DSAEK or PKP was performed. The primary outcome measure was graft failure. Cox proportional hazard regression and Kaplan-Meier survival analyses were used to compare diabetic versus nondiabetic donor tissue for all keratoplasty cases. Results A total of 183 eyes (136 DSAEK, 47 PKP) were included in the statistical analysis. Among 24 procedures performed using diabetic donor tissue, there were 4 cases (16.7%) of graft failure (3 DSAEK, 1 PKP), and among 159 procedures performed using nondiabetic donor tissue, there were 18 cases (11.3%) of graft failure (12 DSAEK, 6 PKP). Cox proportional hazard ratio of graft failure for all cases comparing diabetic with nondiabetic donor tissue was 1.69, but this difference was not statistically significant (95% confidence interval, 0.56-5.06; P = 0.348). There were no significant differences in Kaplan-Meier curves comparing diabetic with nondiabetic donor tissue for all cases (P = 0.380). Statistical analysis of graft failure by donor diabetes status within each procedure type was not possible because of the small number of graft failure events involving diabetic tissue. Conclusions We found similar rates of graft failure in all keratoplasty cases when comparing tissue from diabetic and nondiabetic donors, but further investigation is needed to determine whether diabetic donor tissue results in different graft failure rates after DSAEK compared with PKP.

The corneal endothelium is critical in maintaining a healthy and clear cornea. Corneal endothelial cells have a significant reserve function, but preservation of these cells is paramount as they have limited regenerative capacity. Glaucoma is a prevalent disease, and damage to the corneal endothelium may be caused by the disease process itself as well as by its treatment. The mechanisms involved in glaucoma-associated damage to the corneal endothelium need further investigation. Understanding how glaucoma and glaucoma surgery impact the endothelium is important for protecting corneal clarity and visual acuity in all glaucoma patients, including those undergoing corneal transplant. We will discuss a range of identified factors that may impact corneal endothelial cell health in glaucoma, including intraocular pressure, glaucoma medications, surgical glaucoma management, mechanical forces, and alterations in the aqueous environment.

The aim of this study was to evaluate preparation outcomes of tissue prepared for Descemet membrane endothelial keratoplasty (DMEK) from diabetic and nondiabetic donors.In this nonrandomized, consecutive case series, DMEK grafts were prepared from diabetic and nondiabetic donors by experienced technicians in 2 eye banks using slightly different, modified submerged manual preparation techniques to achieve "prestripped" graft tissue. Graft preparation results were analyzed retrospectively. The main outcome measure was the rate of unsuccessful (failed) DMEK graft preparations, defined as tears through the graft area that prevent tissue use.A total of 359 corneas prepared from 290 donors (114 diabetic and 245 nondiabetic) were included in the statistical analysis of graft preparation failure. There were no significant differences between diabetic and nondiabetic donor tissue characteristics with respect to donor age, death to preservation time, death to preparation time, endothelial cell density, percent hexagonality, or coefficient of variation. DMEK tissue preparation was unsuccessful in 19 (5.3%) cases. There was a significant difference in the site-adjusted rate of DMEK preparation failure between diabetic [15.3%; 95% confidence interval (CI), 9.0-25.0] and nondiabetic donors (1.9%; 95% CI, 0.8-4.8), and the corresponding site-adjusted odds ratio of DMEK graft preparation failure in diabetic donor tissue versus nondiabetic donor tissue was 9.20 (95% CI, 2.89-29.32; P = 0.001).Diabetes may be a risk factor for unsuccessful preparation of donor tissue for DMEK. We recommend caution in the use of diabetic tissue for DMEK graft preparation. Further study is needed to identify what subset of diabetic donors is at risk for unsuccessful DMEK graft preparation.

To evaluate the outcome of the Boston type 1 keratoprosthesis (Kpro-1) in eyes with failed interventions for chemical and thermal injury.A retrospective review was performed of every eye with chemical or thermal injury that was treated with a Kpro-1 at a tertiary eye care center between January 1, 2008 and July 1, 2013. The main outcome measures were visual outcome, prosthesis retention, and postoperative complications.Nine eyes met the inclusion criteria, including 7 eyes with alkali burns, 1 eye with an acid burn, and 1 eye with a thermal burn. After a mean follow-up of 40.7 months (range, 29-60 months), the median best-corrected visual acuity was 20/60 (range, 20/15 to no light perception). One eye was ≥20/20, 3 eyes were ≥20/40, and 6 eyes were ≥20/70. The initial Kpro-1 prosthesis was retained in 7 (77.7%) eyes and successfully replaced in the other 2 eyes. One or more serious complications occurred in 6 (66.7%) eyes. These included 2 cases of sterile corneal ulceration with prosthesis extrusion, 2 cases of microbial keratitis (1 bacterial and 1 fungal), 2 cases of bacterial endophthalmitis, and 2 cases of retinal detachments. These complications contributed to visual outcomes of hand motions in 2 eyes and no light perception in 1 eye.The Boston Kpro-1 is associated with highly satisfactory visual outcomes and prosthesis retention in most cases of severe chemical or thermal injury. Serious complications are common and may compromise the final outcome.

Purpose The aim of this study was to evaluate and compare the outcomes of Boston keratoprosthesis type 1 (Kpro-1) in eyes with herpes simplex virus (HSV) and herpes zoster virus (HZV) keratopathy. Methods A retrospective review was performed of the medical records of every patient treated with a Boston Kpro-1 at the University of Iowa Hospitals and Clinics between January 1, 2008 and July 1, 2012. Eyes with visual loss due to HSV or HZV keratopathy were included in the statistical analysis. The main outcome measures were graft retention, postoperative complications, and visual outcome. Results Nine eyes met the inclusion criteria, including 5 eyes in the HSV group and 4 eyes in the HZV group. The graft retention rate was 100% in the HSV group after a mean follow-up of 48.4 months, compared with 25% in the HZV group after 50.5 months (P = 0.048). There were 3 cases of microbial keratitis, including 2 eyes that also developed endophthalmitis, in the HZV group, compared with no cases in the HSV group (P = 0.048). There was significantly better best-corrected visual acuity at the most recent examination in the HSV group than in the HZV group (P = 0.019). All 5 HSV eyes had improved best-corrected visual acuity compared with preoperative acuity, whereas only 1 HZV eye experienced a similar result (P = 0.048). Conclusions Kpro-1 is associated with an excellent prognosis for graft retention, acceptably low prevalence of sight-threatening complications, and highly satisfactory visual improvement in eyes with HSV keratopathy, but not in eyes with HZV keratopathy.

BACKGROUND CONTEXT Lumbar degenerative disc disease contributes to chronic back pain. Mechanisms of intradiscal degeneration have been linked to genetic, metabolic and mechanical imbalance. Symptomatic relief is influenced by meaningful repair of the annulus and by nucleus supplementation. PURPOSE A protocol was developed to determine whether a cellular allograft disc matrix could be used to augment tissue lost to degeneration. STUDY DESIGN/SETTING A prospective, randomized three-arm study was designed. Following IRB approval, safety and efficacy of disc augmentation was evaluated at 6 and 12 months. (ClinicalTrials.gov NCT03709901). PATIENT SAMPLE This study assesses the first 24 subjects enrolled for safety and efficacy at six and 12 months following the index procedure. Subjects were randomized to receive supplemental allograft consisting of cellularized nucleus pulposus, placebo, or to continue in conservative care. Patients received intradiscal injections in one or two levels. Those subjects who continued conservative care were offered the option to cross over to the allograft at three months if they had no improvement. The first 24 subjects returned one month after transplant. Subjects consisted of five females and 19 males; demographics of age 35.7 (27-62), and BMI 27 (17.7-35.4) were similar between the groups. The safety committee evaluated complications including infections, inflammation, additional interventions and reviewed MRI studies up to 12 months following tissue implantation. Distribution of the subjects were active allograft (16), placebo (4) and continued conservative care (4). OUTCOME MEASURES Visual Analog Scale (VAS), both back and leg, and Oswestry Disability Index (ODI) were the primary symptomatic assessments at one month, six months and 12 months. METHODS The primary outcome of the study evaluated Oswestry Disability Index (ODI) at 6 and 12 months after transplant, and the VAS of Pain Intensity (VASPI) at 6 and 12 months following allograft supplementation. Safety was assessed by the incidence and severity of adverse events (AEs) and clinically relevant changes in laboratory tests. RESULTS Twelve-month data on the first 24 subjects enrolled in the clinical study demonstrated that percutaneous disc intervention can be done safely using a viscous cellular allograft material. No subjects left the study, no adverse events were reported and all conservative care patients crossed over. Back pain, as measured by VAS was reduced in all subjects treated. Mean pain score outcomes of all randomized groups showed symptomatic relief. Allograft pain scores decreased from 58.3 to 9.85 (mean of 48.45); placebo (saline) decreased from 60 to 27.0 (mean of 33.0); and conservative care cross-over to allograft decreased from 55.0 to 6.0 (mean of 49). ODI improved in all subjects in the study. The allograft patients decreased from 54.67 to 12.85 (mean of 41.82); saline patients decreased from 50.40 to 17.50 (mean of 32.90); and conservative care cross-over patients decreased from 65.5 to 20.0 (mean of 45.5). CONCLUSIONS Allograft was well tolerated and demonstrated the greatest amount of symptom relief, provided the most improvement in ODI, and following crossover was able to achieve comparable symptomatic relief despite conservative care having been extended an additional three months. Allograft augmentation offered a safe and effective percutaneous treatment to decrease pain and improve function. FDA DEVICE/DRUG STATUS Unavailable from authors at time of publication.

Purpose To evaluate the outcomes of medical and surgical management of fungal keratitis at a tertiary care eye center. Methods A retrospective review was performed of the medical records of all patients with a diagnosis of microbiologically or histopathologically confirmed fungal keratitis at the University of Iowa Hospitals and Clinics from July 1, 2001, through June 30, 2011. The main outcome measure was a microbiological cure with either medical therapy alone or medical therapy combined with therapeutic keratoplasty (TKP). The secondary outcome measures were graft survival of the TKPs and subsequent optical keratoplasties (OKPs) and visual outcome. Results Seventy-three eyes met the inclusion criteria. A microbiological cure was achieved in 72 eyes (98.6%). Forty-one eyes (56.2%) were treated with medical therapy alone, and 32 (43.8%) eyes required 1 TKP (29 eyes) or 2 TKPs (3 eyes). Among the 32 eyes treated with TKP, 17 (53.1%) maintained a clear graft. Among 15 eyes with failed grafts, 12 eyes ultimately achieved clear grafts after a total of 19 OKP procedures. Among 41 eyes treated with medical therapy alone, all 3 eyes treated with OKP remained clear. The final median best-corrected visual acuity was 20/30 in the medical therapy group and 20/40 in the TKP group. Conclusions A high microbiological cure rate can be achieved in eyes with fungal keratitis; however, TKP is often needed to achieve this objective. A good final visual outcome can be achieved in most cases, but multiple keratoplasty procedures may be required.

To evaluate the efficacy, refractive predictability and stability, and complications of photorefractive keratectomy (PRK) with adjunctive mitomycin C (MMC) in patients with postkeratoplasty anisometropia.A retrospective review was carried out of all cases of PRK performed for postkeratoplasty anisometropia with the VISX Star S4 excimer laser with MMC between January 1, 2004, and December 31, 2008. The main outcome measures were best spectacle-corrected distance visual acuity (CDVA) and patient tolerance of full spectacle refractive correction. Secondary outcome measures were uncorrected distance visual acuity (UDVA), refractive accuracy and stability, and complications.Twenty cases met the inclusion criteria. At 6 months, the spectacle CDVA had improved from a preoperative mean of 20/50 to 20/30 (P = 0.01). Ten eyes (50%) gained 2 or more lines of CDVA. Eighteen eyes (90%) had a CDVA of 20/40 or better. All 20 patients (100%) were subjectively satisfied with full binocular spectacle correction. There was an improvement in UDVA from a preoperative mean of 20/282 to 20/52 (P0.001). Thirteen patients (65%) had an UDVA of 20/40 or better. There was a reduction in the mean refractive spherical equivalent from -5.2 to -0.9 diopters (D), in myopia from -7.6 to -1.8 D, and in astigmatism from 4.9 to 2.0 D. No significant change in visual acuity or refractive error occurred between 3 and 12 months. No sight-threatening complications occurred. One eye (5%) lost 2 lines of CDVA.PRK with adjunctive MMC is an effective method of reducing postkeratoplasty anisometropia and providing satisfactory spectacle rehabilitation.

PURPOSE To determine the visual outcomes, device retention, and complications after Boston type 1 keratoprosthesis (KPro-1) device implantation. METHODS Comprehensive review of every case of KPro-1 implantation at a tertiary eye care center. RESULTS The initial KPro-1 procedure, performed in 75 eyes without a previous keratoprosthesis, was included in the analysis. During the first 6 postoperative months, improvement occurred in the mean preoperative best-corrected visual acuity of 20/1265 to a mean best-obtained postoperative visual acuity of 20/97 (P < 0.001). After a mean follow-up period of 41.4 months (range, 0.8-82.8 months), the final mean best-corrected visual acuity was 20/428. Improved vision was recorded in 43 eyes (57.3%), ambulatory vision (≥20/400) in 47 eyes (62.7%), intermediate functional vision (≥20/80) in 23 eyes (30.7%), and full functional vision (≥20/40) in 11 eyes (14.7%). The initial device was retained in 64 eyes (85.3%), with a Kaplan-Meier retention probability of 96% at 6 months and 82% at 5 years. One or more sight-threatening complications occurred in 51 eyes (68%). These included device extrusion in 11 eyes (14.7%), ulcerative keratitis in 12 eyes (16%), endophthalmitis in 7 eyes (9.3%), sterile vitritis in 3 eyes (4%), retroprosthetic membranes in 25 eyes (33.3%), maculopathy in 26 eyes (34.7%), retinal detachment in 9 eyes (12%), and progressive optic neuropathy in 7 eyes (9.3%). CONCLUSIONS Boston KPro-1 implantation is associated with satisfactory visual outcomes and excellent device retention in a majority of cases. However, serious postoperative complications are common and may compromise the final visual result.

Deer mice (Peromyscus maniculatus) are the main reservoir host for Sin Nombre virus, the primary etiologic agent of hantavirus pulmonary syndrome in North America. Sequential changes in weather and plant productivity (trophic cascades) have been noted as likely catalysts of deer mouse population irruptions, and monitoring and modeling of these phenomena may allow for development of early-warning systems for disease risk. Relationships among weather variables, satellite-derived vegetation productivity, and deer mouse populations were examined for a grassland site east of the Continental Divide and a sage-steppe site west of the Continental Divide in Montana, USA. We acquired monthly deer mouse population data for mid-1994 through 2007 from long-term study sites maintained for monitoring changes in hantavirus reservoir populations, and we compared these with monthly bioclimatology data from the same period and gross primary productivity data from the Moderate Resolution Imaging Spectroradiometer sensor for 2000–06. We used the Random Forests statistical learning technique to fit a series of predictive models based on temperature, precipitation, and vegetation productivity variables. Although we attempted several iterations of models, including incorporating lag effects and classifying rodent density by seasonal thresholds, our results showed no ability to predict rodent populations using vegetation productivity or weather data. We concluded that trophic cascade connections to rodent population levels may be weaker than originally supposed, may be specific to only certain climatic regions, or may not be detectable using remotely sensed vegetation productivity measures, although weather patterns and vegetation dynamics were positively correlated.

Purpose: To evaluate and compare the outcome of initial resident surgical experience with photorefractive keratectomy (PRK) and LASIK. Methods: Retrospective review of all cases performed with the VISX Star S4 platform (Abbott Medical Optics) between July 1, 2003 and June 30, 2007. Inclusion criteria were spherical equivalent of −0.50 to −10.00 diopters (D), refractive astigmatic error of ≤3.00 D, intention to provide full distance correction, and minimum 3-month postoperative follow-up after initial ablation or retreatment (if performed). Results: A total of 153 cases performed by 20 different residents met the inclusion criteria; 38 eyes underwent PRK and 115 eyes had LASIK. After initial treatment, mean Snellen uncorrected distance visual acuity (UDVA) after PRK was 20/17.3 and after LASIK was 20/19.5. Photorefractive keratectomy was associated with a significantly better approximation between preoperative corrected distance visual acuity (CDVA) and postoperative UDVA (ΔlogMAR 0.009 vs 0.091; P =.004) and a greater percentage of eyes that achieved UDVA of 20/20 or better (94.7% vs 78.3%; P =.02) or 20/30 or better (100% vs 87.8%; P =.02). There was a higher prevalence of retreatment in eyes that underwent LASIK (7.0% vs 0%; P =.20). One (0.9%) eye lost 2 lines of CDVA after LASIK. Conclusions: Supervised refractive surgery residents can achieve excellent visual outcomes in patients operated during their initial refractive experience. Photorefractive keratectomy was associated with better visual outcome than LASIK.

Purpose To determine the prevalence and risk factors for escalation of glaucoma therapy after deep lamellar endothelial keratoplasty (DLEK). Methods Retrospective review of every case of DLEK performed at a tertiary care facility between December 1, 2003 and January 31, 2006. Results Eighty eyes met the inclusion criteria. Escalation of glaucoma therapy occurred in 13 eyes (16.3%) during a mean follow-up period of 27.1 months. Ten eyes required additional topical medical therapy, and 3 eyes required surgical intervention. Glaucoma therapy escalation was significantly associated with preexisting glaucoma (42.9% vs. 10.6%; P = 0.008). Conclusion Escalation of glaucoma therapy is not uncommon after DLEK, especially in eyes with preexisting glaucoma.

PURPOSE To evaluate the outcome of primary adult optical penetrating keratoplasty (PKP) in a Saudi Arabian population. PATIENTS AND METHODS A retrospective review was performed of the medical records of every Saudi Arabian patient 12 years of age or older who underwent PKP for keratoconus, corneal edema, stromal scarring, or stromal dystrophy at King Khaled Eye Specialist Hospital between January 1, 1997, and December 31, 2001, and for whom a minimum of 3 months of follow-up was available. RESULTS Of 910 eyes that met the inclusion criteria, there were 464 eyes with keratoconus, 188 eyes with corneal edema, 175 eyes with stromal scarring, and 83 eyes with stromal dystrophy. The 5-year survival probability was 96.1% for keratoconus, 71.1% for stromal scarring, 85.9% for stromal dystrophy, and 40.3% for corneal edema. The most significant risk factor affecting graft survival was surgical indication (P < 0.001). Among eyes with corneal edema, increasing donor age (P = 0.004) and the occurrence of one or more complications (P < 0.001) were significantly associated with an increased risk of graft failure. Overall, improvement in vision occurred in 750 (82.4%) eyes, remained the same in 97 (10.7%) eyes, and worsened in 63 (6.9%) eyes. CONCLUSION In the Saudi Arabian population, the prognosis for graft survival and improved visual acuity is excellent for eyes with keratoconus and stromal dystrophy, good for stromal scarring, and poor for eyes with corneal edema.

To report 2 cases of donor-to-host transmission of Candida albicans interface keratitis after Descemet stripping automated endothelial keratoplasty (DSAEK).We performed clinical and microbiologic examinations on 2 patients who underwent DSAEK for pseudophakic corneal edema.Two patients underwent uneventful DSAEK surgery using corneal tissue from the same donor. The donor corneoscleral rims were cultured at the time of surgery and both rims subsequently grew C. albicans and Candida glabrata. Approximately 5 weeks after surgery, infiltrates were noted in the DSAEK interface in both of these patients. Despite treatment with antifungal therapy, the Candida keratitis was unable to be controlled medically and required surgical intervention in each case, after which there was no recurrence of infection.Candida interface keratitis can occur after DSAEK. These 2 cases emphasize the importance of donor corneoscleral rim cultures, especially with the increase in lamellar and endothelial keratoplasty, which can make such interface infections more difficult to diagnose and treat. Patients with fungal positive donor corneal rim cultures should be prophylactically treated with antifungal therapy.

Extensive clinical and experimental evidence has suggested a role for corneal epithelium, keratocytes, and acute inflammatory cells in sterile corneal ulceration, although the precise role of these cell types in stromal matrix degradation has not been elucidated. We studied two corneal buttons and two whole corneas from 4 patients with corneal grafts and sterile stromal ulceration. Each cornea was divided into several sections and examined morphologically, while adjacent sections were placed in tissue culture and assayed for collagenase activity against type I collagen. In each case, collagenase activity was present in tissue from ulcerating and nonulcerating areas and, in most regions assayed, exceeded collagenase activity in normal control peripheral donor corneas. Collagenase levels were not always greatest in areas of most advanced ulceration. Although polymorphonuclear leukocytes were extensively present histologically in two cases, one case had a mixed inflammatory cell population at the site of ulceration, and another had only keratocytes (fibroblasts) present in the entire cornea. We conclude that regional differences in collagen degradation are due not only to the presence of collagenase, but also to cellular and humoral activators and inhibitors that determine collagenolytic activity.

PURPOSE To evaluate the prevalence of postoperative complications and their impact on graft survival after primary adult optical penetrating keratoplasty (PKP). METHODS A retrospective review was done of consecutive cases of PKP performed between January 1, 1997, and December 31, 2001, for keratoconus, corneal edema, stromal scarring, and stromal dystrophy. RESULTS The inclusion criteria were met by 910 eyes, including 464 with keratoconus, 188 with corneal edema, 175 with stromal scarring, and 83 with stromal dystrophy. One or more complications occurred in 362 eyes (39.8%). The most common complication was endothelial rejection (17.3%), followed by glaucoma worsening (15.5%), bacterial keratitis (5.8%), persistent epithelial defects (3.4%), and wound dehiscence (1.6%). There were significant differences among the surgical groups in overall prevalence of complications (P < 0.001) and with the prevalence of endothelial rejection (P = 0.01), glaucoma worsening (P < 0.001), bacterial keratitis (P = 0.04), and persistent epithelial defects (P = 0.02). Complication-associated graft failure varied significantly among the surgical groups (P = 0.02). CONCLUSION The prevalence of post-PKP complications and their impact on graft survival vary significantly among surgical indications for primary adult optical PKP.

Purpose The purpose of this study was to evaluate graft survival, postoperative complications, and visual outcome after penetrating keratoplasty (PKP) for keratoconus (KC) in eyes with or without a history of vernal keratoconjunctivitis (VKC). Methods A retrospective review was conducted on all cases of PKP performed at King Khaled Eye Specialist Hospital between January 1, 1997, and December 31, 2001, for KC. Results Four hundred sixty-four eyes were included in the study, including 80 (17.2%) eyes with VKC and 384 (82.8%) without VKC. Five-year graft survival was 97.3% and 95.5% in eyes with or without VKC, respectively. There were no statistically significant differences in Kaplan-Meier graft survival between the 2 groups at any time interval. There were no statistically significant differences in the percentage of eyes experiencing postoperative complications in eyes with or without VKC (27.5% vs 31.8%, respectively; P = 0.50). However, late-onset persistent epithelial defects were significantly more likely to occur in eyes with VKC (6.3% vs 1.8%; P = 0.04). There were no significant differences in the prevalence of endothelial rejection, bacterial keratitis, glaucoma, wound dehiscence, early-onset persistent epithelial defects, or secondary cataract. The median final best-corrected visual acuity was 20/30 in both groups. The percentage of eyes with a final best-corrected visual acuity of 20/40 or better was 76.2% in eyes with VKC and 71.9% in eyes without VKC (P = 0.49). Conclusions Graft survival, postoperative complications, and visual outcome are comparable after PKP for KC in eyes with or without VKC.

PURPOSE To compare central corneal endothelium cell density and morphology in eyes with keratoconus and unilateral resolved hydrops with the unaffected fellow eye. METHODS Bilateral confocal microscopy was performed 3 months after resolution of acute unilateral hydrops in patients with keratoconus who presented to the King Khaled Eye Specialist Hospital between February 1, 2004, and November 31, 2005. RESULTS Twenty-six patients (19 men and 7 women) with a mean age of 22 years (range, 11-36 years) were enrolled in the study. A history of ocular allergy or rigid gas-permeable hard contact lens wear was present in 14 and 12 patients, respectively. The mean interval to resolution of hydrops was 12 weeks (range, 9-14 weeks), after which neovascularization was present in 8 eyes. The mean endothelial cell density in affected and unaffected eyes was virtually identical (2759 vs. 2788 cells/mm2, respectively; P = 0.82), although 5 (19.2%) affected eyes did have endothelial cell density that was >15% less than that of the unaffected fellow eye. Compared with unaffected eyes, there was a mean increase polymegathism in affected eyes from 33% to 35% and a mean decrease in hexagonality from 60% to 55%, but these differences were not statistically significant (P = 0.11 and 0.06, respectively). CONCLUSIONS Decreased endothelial cell density is uncommon after resolution of acute hydrops, although morphologic changes may be present in a majority of cases.

Patients in Goalando were likely infected by direct contact with fruit bats or their secretions, rather than through contact with an intermediate host., Nipah virus (NiV) is a paramyxovirus that causes severe encephalitis in humans. During January 2004, twelve patients with NiV encephalitis (NiVE) were identified in west-central Bangladesh. A case–control study was conducted to identify factors associated with NiV infection. NiVE patients from the outbreak were enrolled in a matched case-control study. Exact odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by using a matched analysis. Climbing trees (83% of cases vs. 51% of controls, OR 8.2, 95% CI 1.25–∞) and contact with another NiVE patient (67% of cases vs. 9% of controls, OR 21.4, 95% CI 2.78–966.1) were associated with infection. We did not identify an increased risk for NiV infection among persons who had contact with a potential intermediate host. Although we cannot rule out person-to-person transmission, case-patients were likely infected from contact with fruit bats or their secretions.

To determine the prevalence and risk factors for escalation of glaucoma therapy after penetrating keratoplasty (PK) and its impact on graft survival and visual outcome.Retrospective case series.Seven hundred fifteen consecutive eyes of 678 patients undergoing PK.Retrospective review of every case of PK performed at King Khaled Eye Specialist Hospital between January 1, 2001 and December 31, 2002.Escalation of glaucoma therapy, graft survival, and visual outcome.Escalation of glaucoma therapy occurred in 89 (12.4%) eyes of 715 PK procedures during a mean follow-up of 32.2 months. Medical escalation accounted for 73 (82.0%) cases, whereas surgical escalation occurred in 16 (18.0%) eyes. The following were significantly associated with an increased risk of escalation of glaucoma therapy: surgical indication for PK (P0.001), increasing patient age (P0.001), preexisting glaucoma (P0.001), recipient trephination7.0 mm (P = 0.02), and pseudophakia or aphakia (P0.001). Eyes with escalation of glaucoma therapy had significant reduction in graft survival compared with eyes in which this did not occur (52.8% vs. 82.9%, P0.001). Escalation of glaucoma therapy was associated with a significant reduction in the percentage of eyes achieving visual acuity of 20/40 or better (9.0% vs. 42.1%, P0.001) and a significant increase in those obtaining 20/200 or worse (70.8% vs. 26.7%, P0.001).Escalation of glaucoma therapy is a serious sequela of PK that is significantly associated with an increased risk of graft failure and poor visual outcome.

American hantaviruses cause a severe respiratory disease known as hantavirus pulmonary syndrome (HPS). In the United States, Sin Nombre virus (SNV), carried by the deer mouse ( Peromyscus maniculatus), is the etiologic agent in the majority of HPS cases. The relationship between deer mouse population density and SNV infection prevalence in deer mice is poorly understood. Our purpose was to clarify this relationship by demonstrating the existence of delayed-density-dependent prevalence of SNV infection in populations of wild deer mice. We also explored the relationship between SNV infection in deer mouse populations and the incidence of human HPS. The study population was 3,616 deer mice captured on 10 mark-recapture grids in Montana during May and September, 1994-2004. Using multivariate logistic regression analysis, we found a strong association between deer mouse population density in fall (September) and SNV antibody prevalence in deer mice the following spring (May). Other characteristics associated with SNV infection in deer mice in spring were: (1) presence of at least one infected deer mouse in the population the previous fall, (2) male gender, (3) adult age class, (4) presence of scars, (5) grassland and logged habitats, and (6) elevations below 1,300 m. There was a strong association between concurrently measured SNV antibody prevalence in deer mice and probable exposure of human HPS cases during the same time period. Human cases were more likely to occur during seasons when SNV antibody prevalence was at least 10% in deer mouse populations. These findings suggest that fall rodent population parameters could be used to help guide prevention efforts the following spring.

A unique strain of this virus was traced back to hamsters from an Ohio rodent distribution facility., In April 2005, 4 transplant recipients became ill after receiving organs infected with lymphocytic choriomeningitis virus (LCMV); 3 subsequently died. All organs came from a donor who had been exposed to a hamster infected with LCMV. The hamster was traced back through a Rhode Island pet store to a distribution center in Ohio, and more LCMV-infected hamsters were discovered in both. Rodents from the Ohio facility and its parent facility in Arkansas were tested for the same LCMV strain as the 1 involved in the transplant-associated deaths. Phylogenetic analysis of virus sequences linked the rodents from the Ohio facility to the Rhode Island pet store, the index hamster, and the transplant recipients. This report details the animal traceback and the supporting laboratory investigations.

We characterized mitochondrial respiration and glycolysis activity of human corneal endothelium, and compared metabolic activity between central and peripheral regions.Endothelial keratoplasty-suitable corneas were obtained from donors aged 50 to 75 years. The endothelium-Descemet membrane complex (EDM) was isolated, and 3-mm punches were obtained from central and peripheral regions. Endothelium-Descemet membrane punches were assayed for mitochondrial respiration (oxygen consumption) and glycolysis (extracellular acidification) using an extracellular flux analyzer. Enzymatic (citrate synthase, glucose hexokinase) and mitochondrial density (MitoTracker) assays also were performed.Ten corneas were analyzed per assay. Metabolic activity for mitochondrial respiration and glycolysis showed expected changes to assay compounds (P0.01, all pairwise comparisons). Basal mitochondrial respiration and glycolysis activity did not differ between regions (P0.99). Similarly, central versus peripheral activity after assay compound treatment showed no significant differences (P0.99, all time points). The intracorneal coefficient of variation for basal readings between two and four peripheral punches was 18.5% of the mean. Although peripheral samples displayed greater enzymatic activity than central samples (P0.05), similar to extracellular flux results, mitochondrial density did not differ between regions (P = 0.78).Extracellular flux analysis of oxygen and pH is a valid technique for characterizing metabolic activity of human corneal endothelium. This technique demonstrates high reproducibility, allows quantification of metabolic parameters using small quantities of live cells, and permits estimation of overall metabolic output. Neither oxygen consumption nor extracellular acidification differed between central and peripheral regions of transplant suitable corneas in this series. Our results show that endothelial cell health can be quantified biochemically in transplant suitable corneas.

Background/aims To evaluate the Boston type 1 keratoprosthesis (KPro-1) in treatment of eyes with primary congenital glaucoma. Methods A retrospective review was performed of every eye with congenital glaucoma that was treated with a KPro-1 at a tertiary eye care centre between 1 January 2008 and 1 July 2014. The main outcome measures were visual outcome, prosthesis retention and postoperative complications. Results Six eyes of six patients met the inclusion criteria. This included two paediatric patients, aged 6 months and 6 years, and four adults who were 27–33 years of age. Preoperatively, the best corrected visual acuity (BCVA) was worse than 20/400 in every eye. Three eyes had hand motions and one eye had light perception vision. After a mean follow-up period of 31 months (range 16–51 months), three eyes (50.0%) had a BCVA that was ≥20/400. Overall, the BCVA improved in four eyes (66.7%), and remained the same in two eyes (33.3%). The device was retained in six eyes (83.3%). One or more complications occurred in five eyes (83.3%) and included sterile corneal ulceration (three eyes), retroprosthetic membrane formation (three eyes), progressive glaucomatous optic neuropathy (two eyes), device extrusion (one eye) and an epiretinal membrane (one eye). Conclusions The Boston KPro-1 has an excellent prognosis for retention in eyes with congenital glaucoma. The visual prognosis remains guarded due to the high prevalence of pre-existing ocular comorbidity and the common occurrence of sight-threatening postoperative complications.

Objective This document evaluates currently available data in the published literature to answer the question of whether the use of dye such as indocyanine green or trypan blue to stain the lens capsule to improve visualization is safe and effective as an adjunct to cataract surgery. Methods Literature searches conducted in March 2003 and May 2004 retrieved 139 citations. The panel members reviewed the abstracts and selected 47 of possible clinical relevance for review. An additional 14 articles were identified for evaluation. Of the 61 articles reviewed, the panel members selected 36 for the panel methodologist to review and rate according to the strength of the evidence. A level I rating was assigned to properly conducted, well-designed, randomized clinical trials; a level II rating was assigned to well-designed cohort and case–control studies; and a level III rating was assigned to case series and case reports. Results There is level III evidence that indocyanine green, trypan blue, and fluorescein are each effective in staining the lens capsule and that indocyanine green and trypan blue provide better ease of use and visualization of the capsule than fluoroscein. There is level II evidence that staining the capsule is helpful in completing capsulorrhexis and that it is helpful for pediatric patients under age 5 years and in cases of white cataract. The overall surgical advantage of a completed continuous curvilinear capsulorrhexis using dye has not been demonstrated, but this may be related to the outcome measures chosen rather than a failure to confer advantage. There are substantial data indicating that trypan blue 0.1% is not toxic to the cornea. There are limited data suggesting that indocyanine green 0.125% to 0.5% is not toxic to anterior segment structures. Conclusions There are data confirming that dye is safe and effective as an adjunct for capsule visualization in cataract surgery. It is reasonable to use dye when inadequate capsule visualization may compromise the outcome in cataract surgery. More studies are needed to confirm a lack of toxicity of indocyanine green and trypan blue, particularly in the event of posterior segment or longer duration exposure.

We applied a rigorous, quantitative methodology to the analysis of local-scale spatial clustering of multiple murid mice (brush mice, Peromyscus boylii; deer mice, P. maniculatus; pinon mice, P. truei; western harvest mice, Reithrodontomys megalotis) infected or uninfected with hantaviruses. Rodents were sampled longitudinally from 1994 to 2001 on 23 trapping webs at 10 locations in the southwestern United States. This study provided an opportunity to apply meta-analysis techniques to an important ecological question. There were sufficient captures by species on 199 occasions (three consecutive nights) to compare general use of space using multi-response permutation procedures (MRPP). The MRPP results were then used in meta-analyses by species to determine if overall effects of spatial clustering of hantavirus-infected mice as well as categorical effects (elevation, season, site, and state) were present. Based on MRPP analyses, overall spatial clustering of hantavirus-infected mice was most pronounced for brush mice, followed by the deer mouse. Meta-analyses indicated significant overall effects of spatial clustering and varying categorical effects (elevation, season, site, state) of infected mice for each species compared. The overlapping space use by rodents might be an important factor affecting the local transmission of several hantaviruses.

Peripheral blood samples obtained from patients during an outbreak of Ebola virus (Sudan species) disease in Uganda in 2000 were used to phenotype peripheral blood mononuclear cells (PBMC), quantitate gene expression, measure antigenemia, and determine nitric oxide levels. It was determined that as the severity of disease increased in infected patients, there was a corresponding increase in antigenemia and leukopenia. Blood smears revealed thrombocytopenia, a left shift in neutrophils (in some cases degenerating), and atypical lymphocytes. Infected patients who died had reduced numbers of T cells, CD8 + T cells, and activated (HLA-DR + ) CD8 + T cells, while the opposite was noted for patients who survived the disease. Expression levels of cytokines, Fas antigen, and Fas ligand (TaqMan quantitation) in PBMC from infected patients were not significantly different from those in uninfected patients (treated in the same isolation wards), nor was there a significant increase in expression compared to healthy volunteers (United States). This unresponsive state of PBMC from infected patients despite high levels of circulating antigen and virus replication suggests that some form of immunosuppression had developed. Ebola virus RNA levels (virus load) in PBMC specimens were found to be much higher in infected patients who died than patients who survived the disease. Similarly, blood levels of nitric oxide were much higher in fatal cases (increasing with disease severity), and extremely elevated levels (≥150 μM) would have negatively affected vascular tone and contributed to virus-induced shock.

Objective This review was conducted to determine the safety and efficacy of open-loop anterior chamber, scleral-sutured posterior chamber, and iris-sutured posterior chamber intraocular lenses (IOLs) in eyes with inadequate capsular support for posterior chamber implantation in the capsular bag or ciliary sulcus. It also attempted to determine whether there is a preferred IOL or fixation site of choice in eyes with inadequate capsular support. Methods A literature search conducted for the years 1980 to 2001 yielded 189 citations related to IOL implantation in the absence of capsular support. An update search, conducted in March 2002, yielded an additional 28 articles. The Anterior Segment Panel members reviewed these abstracts and selected 148 articles of possible clinical relevance for review. Of these, 89 were considered sufficiently clinically relevant for the panel methodologist to review and rate according to the strength of evidence. A level I rating was assigned to properly conducted, well-designed, randomized clinical trials; a level II rating was assigned to well-designed cohort and case-control studies; and a level III rating was assigned to case series. Articles comparing the safety and efficacy of the IOL type and fixation site were further evaluated for the quality of the statistical methods used in the study. Studies with a rating of A or B were considered acceptable, C was borderline, and D and F were considered unacceptable as medical evidence. Results Forty-three articles with data concerning outcome of IOL insertion in eyes with inadequate capsular support had an evidence rating of level III or higher and were used in the final review of the safety and efficacy of one or more lens types and/or fixation sites. Seven articles had data about more than one lens type. Six had a statistical method rating of C or higher and were used to evaluate differences in visual outcomes and complication rates between lens types and fixation sites. Conclusions The literature supports the safe and effective use of open-loop anterior chamber, scleral-sutured posterior chamber, and iris-sutured posterior chamber IOLs for the correction of aphakia in eyes without adequate capsular support for placement of a posterior chamber lens in the capsular bag or ciliary sulcus. At this time, there is insufficient evidence to demonstrate the superiority of one lens type or fixation site. Precise determination of small differences in visual outcome or complication rates will require a large prospective, randomized clinical trial.

Purpose: To determine the role of the single nucleotide polymorphism (SNP) (rs613872) in the TCF4 gene in Fuchs endothelial corneal dystrophy (FECD) in patients from Iowa.Methods: A cohort of 82 patients with FECD and 163 normal control subjects from Iowa were genotyped at the SNP rs613872 using a real-time allelic discrimination assay.Results: The frequencies of the alleles of rs613872 were compared between FECD patients and control subjects. A highly significant association (p-value = 2.96 × 10−10) was detected between this SNP and FECD. Comparison of the genotypes of SNP rs613872 between FECD patients and control subjects produced a p-value of 2.43 × 10−10.Conclusion: Prior reports have shown that SNP rs613872 in the TCF4 gene is highly associated with FECD. Our study confirms this association and shows that the TCF4 gene has an important role in the pathogenesis of corneal disease in patients from Iowa.

To describe the clinical course of a patient requiring ophthalmic care for entropion and fungal keratitis in the setting of undiagnosed enophthalmos after previous ventriculoperitoneal shunting consistent with silent brain syndrome.Case report.A 33-year-old man who had a history of ventriculoperitoneal shunting for an encephalocele during infancy presented because of ocular irritation and entropion, which was presumed to be entirely due to a chemical injury he had sustained 2 years before. He underwent 2 upper eyelid entropion repairs and developed fungal aspergilloma keratitis in the postoperative period. He underwent 2 penetrating keratoplasties and a limbal stem cell transplant but had complications with reinfection of the graft, eventually leading to a prephthisical painful eye. During enucleation, an aspergilloma was found within an enlarged superior fornix. Computed tomographic scan revealed severe enophthalmos with air between the lids and the globe, which was consistent with silent brain syndrome.In patients with silent brain syndrome, the lack of apposition between the eyelids and the globe results in entropion, trichiasis, lagophthalmos, and ocular irritation. This can complicate entropion repair and the severity of infectious keratitis. We also propose that the enlarged fornices seen in silent brain syndrome can also serve as a reservoir for infection, similar to the pathogenesis seen in the giant fornix syndrome.

The short-term prospects for Fermilab experiment E771 - devoted to the hadroproduction of beauty - are described as well as the major characteristics of the spectrometer. Expectations for detection and reconstruction of exclusive B decay channels are discussed.

Purpose The aim of this study was to evaluate the outcome of pretreatment of Acanthamoeba keratitis with intravenous pentamidine (IVP) before therapeutic keratoplasty (TKP). Methods A retrospective chart review was performed of the medical records of every patient treated with IVP before TKP for Acanthamoeba keratitis at a single, tertiary care eye center between January 1, 2002, and December 31, 2012. The main outcome measures were microbiological cure, graft survival, and visual outcome. Results Eight eyes of 7 patients met the inclusion criteria. Preoperatively, all 8 eyes had failed traditional antiamoebic therapy, including 5 eyes with recurrent infections after previous TKP. The patients were treated with IVP (190-400 mg/d) for a median of 14 days (range, 7-26 days). After 8 TKP, a microbiological cure was achieved, and a clear graft was maintained in 5 (62.5%) eyes during a mean follow-up interval of 31.2 months (range, 1.0-95.7 months). Repeat TKP in 3 eyes with recurrent Acanthamoeba keratitis resulted in 2 additional microbiological cures and 1 more clear graft. The final best-corrected visual acuity was ≥20/40 in 5 (62.5%) eyes and worse than 20/200 in 3 eyes. Overall, the final vision was improved in 6 (75.0%) eyes, remained the same in 1 (12.5%) eye, and was worse in 1 (12.5%) eye. Conclusions The adjunctive use of IVP before TKP may assist with the achievement of microbiological cure, clear graft, and good visual outcome in a majority of eyes with Acanthamoeba keratitis.