Growth factor restriction impedes progression of wound healing following cataract surgery: identification of VEGF as a putative therapeutic target

Secondary visual loss occurs in millions of patients due to a wound-healing response, known as posterior capsule opacification (PCO), following cataract surgery. An intraocular lens (IOL) is implanted into residual lens tissue, known as the capsular bag, following cataract removal. Standard IOLs allow the anterior and posterior capsules to become physically connected. This places pressure on the IOL and improves contact with the underlying posterior capsule. New open bag IOL designs separate the anterior capsule and posterior capsules and further reduce PCO incidence. It is hypothesised that this results from reduced cytokine availability due to greater irrigation of the bag. We therefore explored the role of growth factor restriction on PCO using human lens cell and tissue culture models. We demonstrate that cytokine dilution, by increasing medium volume, significantly reduced cell coverage in both closed and open capsular bag models. This coincided with reduced cell density and myofibroblast formation. A screen of 27 cytokines identified nine candidates whose expression profile correlated with growth. In particular, VEGF was found to regulate cell survival, growth and myofibroblast formation. VEGF provides a therapeutic target to further manage PCO development and will yield best results when used in conjunction with open bag IOL designs

Field Evaluation of the Cepheid GeneXpert Chlamydia trachomatis assay for Detection of Infection in a Trachoma Endemic Community in Tanzania.

\ud \ud To determine the sensitivity, specificity, and field utility of the Cepheid GeneXpert Chlamydia trachomatis (CT) Assay (GeneXpert) for ocular chlamydia infection compared to Roche Amplicor CT assay (Amplicor). In a trachoma-endemic community in Kongwa Tanzania, 144 children ages 0 to 9 were surveyed to assess clinical trachoma and had two ocular swabs taken. One swab was processed at Johns Hopkins University, Baltimore MD, using Amplicor, (Roche Molecular Diagnostics) and the other swab was processed at a field station in Kongwa using the GeneXpert Chlamydia trachomatis/Neisseria gonorrhoeae assay (Cepheid). The sensitivity and specificity of GeneXpert was compared to the Amplicor assay. Of the 144 swabs taken the prevalence of follicular trachoma by clinical exam was 43.7%, and by evidence of infection according to Amplicor was 28.5%. A total of 17 specimens (11.8%) could not be processed by GeneXpert in the field due to lack of sample volume, other specimen issues or electricity failure. The sensitivity of GeneXpert when compared to Amplicor was 100% and the specificity was 95%. The GeneXpert test identified more positives in individuals with clinical trachoma than Amplicor, 55% versus 52%. The GeneXpert test for C. trachomatis performed with high sensitivity and specificity and demonstrated excellent promise as a field test for trachoma control.\u

CT694 and pgp3 as Serological Tools for Monitoring Trachoma Programs.

Defining endpoints for trachoma programs can be a challenge as clinical signs of infection may persist in the absence of detectable bacteria. Antibody-based tests may provide an alternative testing strategy for surveillance during terminal phases of the program. Antibody-based assays, in particular ELISAs, have been shown to be useful to document C. trachomatis genital infections, but have not been explored extensively for ocular C. trachomatis infections. An antibody-based multiplex assay was used to test two C. trachomatis antigens, pgp3 and CT694, for detection of trachoma antibodies in bloodspots from Tanzanian children (n = 160) collected after multiple rounds of mass azithromycin treatment. Using samples from C. trachomatis-positive (by PCR) children from Tanzania (n = 11) and control sera from a non-endemic group of U.S. children (n = 122), IgG responses to both pgp3 and CT694 were determined to be 91% sensitive and 98% specific. Antibody responses of Tanzanian children were analyzed with regard to clinical trachoma, PCR positivity, and age. In general, children with more intense ocular pathology (TF/TI = 2 or most severe) had a higher median antibody response to pgp3 (p = 0.0041) and CT694 (p = 0.0282) than those with normal exams (TF/TI = 0). However, 44% of children with no ocular pathology tested positive for antibody, suggesting prior infection. The median titer of antibody responses for children less than three years of age was significantly lower than those of older children. (p<0.0001 for both antigens). The antibody-based multiplex assay is a sensitive and specific additional tool for evaluating trachoma transmission. The assay can also be expanded to include antigens representing different diseases, allowing for a robust assay for monitoring across NTD programs

Elimination of onchocerciasis in Ecuador: findings of post-treatment surveillance.

BACKGROUND: The Esmeraldas focus of onchocerciasis in Ecuador expanded geographically during the 1980s and was associated with severe ocular and skin disease. Mass drug administration (MDA) with ivermectin started in 1991, initially once but later twice a year, in the principle endemic focus followed by all satellite foci. Treatment was stopped in 2009 when entomological assessments determined that transmission of Onchocerca volvulus had been interrupted. METHODS: Three years after the cessation of ivermectin treatment in 2012, as defined by the WHO guidelines for onchocerciasis elimination, blackfly collections were done in four sentinel sites in former hyperendemic areas. The presence of infective larvae in local vectors, Simulium exiguum and Simulum quadrivittatum, was assessed by detection of O. volvulus DNA by PCR. Additional flies captured in four extra-sentinel sites located in former hyper- and mesoendemic dispersed isolated areas were also assessed. RESULTS: The results from 68,310 captured blackflies, 40,114 from four sentinel villages in the previously hyperendemic areas (Corriente Grande, El Tigre, San Miguel on Río Cayapas and Naranjal on Río Canandé) and 28,197 from extra-sentinel locations, were all negative for the presence of O. volvulus. These extra-sentinel sites (Hualpí on Río Hoja Blanca, Capulí on Río Onzole, La Ceiba on Río Tululví and Medianía on Río Verde) were included to provide additional evidence of the impact of MDA on the transmission of O. volvulus in isolated endemic areas. CONCLUSIONS: Our data indicate that transmission of O. volvulus has been stopped in all endemic areas in Ecuador, including all satellite foci outside the main focus. These findings indicate that a strategy of ivermectin distribution twice a year to over 85% of the treatment-eligible population was effective in eliminating the infection from Ecuador in a focus with a highly competent primary vector, S. exiguum, and where the infection rates were equal to or greater than observed in many onchocerciasis foci in Africa

Global prevalence of childhood cataract: a systematic review

Childhood cataract is an avoidable cause of visual disability worldwide and is a priority for VISION 2020: The Right to Sight. There is a paucity of information about the burden of cataract in children and the aim of this review is to assess the global prevalence of childhood cataract. The methodology for the review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed a literature search for studies reporting estimates of prevalence or incidence of cataract among children (aged<18 years) at any global location using the Cochrane Library, Medline and Embase up to January 2015. No restrictions were imposed based on language or year of publication. Study quality was assessed using a critical appraisal tool designed for systematic reviews of prevalence. Twenty prevalence and four incidence studies of childhood cataract from five different geographical regions were included. The overall prevalence of childhood cataract and congenital cataract was in the range from 0.32 to 22.9/10000 children (median=1.03) and 0.63 to 9.74/10000 (median=1.71), respectively. The incidence ranged from 1.8 to 3.6/10000 per year. The prevalence of childhood cataract in low-income economies was found to be 0.42 to 2.05 compared with 0.63 to 13.6/10000 in high-income economies. There was no difference in the prevalence based on laterality or gender. This review highlights substantial gaps in the epidemiological knowledge of childhood cataract worldwide, particularly from low and lower middle-income economies. More studies are needed using standard definitions and case ascertainment methods with large enough sample sizes

Costs of Testing for Ocular Chlamydia trachomatis Infection Compared to Mass Drug Administration for Trachoma in The Gambia: Application of Results from the PRET Study

Background Mass drug administration (MDA) treatment of active trachoma with antibiotic is recommended to be initiated in any district where the prevalence of trachoma inflammation, follicular (TF) is ≥10% in children aged 1–9 years, and then to continue for at least three annual rounds before resurvey. In The Gambia the PRET study found that discontinuing MDA based on testing a sample of children for ocular Chlamydia trachomatis(Ct) infection after one MDA round had similar effects to continuing MDA for three rounds. Moreover, one round of MDA reduced disease below the 5% TF threshold. We compared the costs of examining a sample of children for TF, and of testing them for Ct, with those of MDA rounds. Methods The implementation unit in PRET The Gambia was a census enumeration area (EA) of 600–800 people. Personnel, fuel, equipment, consumables, data entry and supervision costs were collected for census and treatment of a sample of EAs and for the examination, sampling and testing for Ct infection of 100 individuals within them. Programme costs and resource savings from testing and treatment strategies were inferred for the 102 EAs in the study area, and compared. Results Census costs were $103.24 per EA plus initial costs of$108.79. MDA with donated azithromycin cost $227.23 per EA. The mean cost of examining and testing 100 children was$796.90 per EA, with Ct testing kits costing $4.80 per result. A strategy of testing each EA for infection is more expensive than two annual rounds of MDA unless the kit cost is less than$1.38 per result. However stopping or deciding not to initiate treatment in the study area based on testing a sample of EAs for Ct infection (or examining children in a sample of EAs) creates savings relative to further unnecessary treatments. Conclusion Resources may be saved by using tests for chlamydial infection or clinical examination to determine that initial or subsequent rounds of MDA for trachoma are unnecessary

Cross-Sectional Surveys of the Prevalence of Follicular Trachoma and Trichiasis in The Gambia: Has Elimination Been Reached?

BACKGROUND: The Gambia's National Eye Health Programme has made a concerted effort to reduce the prevalence of trachoma. The present study had two objectives. The first was to conduct surveillance following mass drug administrations to determine whether The Gambia has reached the World Health Organization's (WHO) criteria for trachoma elimination, namely a prevalence of trachomatous inflammation-follicular (TF) of less than 5% in children aged 1 to 9 years. The second was to determine the prevalence of trichiasis (TT) cases unknown to the programme and evaluate whether these meet the WHO criteria of less than 0.1% in the total population. METHODOLOGY/PRINCIPAL FINDINGS: Three cross-sectional surveys were conducted between 2011 and 2013 to determine the prevalence of TF and TT in each of nine surveillance zones. Each zone was of similar size, with a population of 60,000 to 90,000, once urban settlements were excluded. Trachoma grading was carried out according to the WHO's simplified trachoma grading system. The prevalence of TF in children aged 1 to 9 years was less than 5% in each surveillance zone at each of the three surveys. The prevalence of TT cases varied by zone from 0 to 1.7% of adults greater than 14 years while the prevalence of TT cases unknown to the country's National Eye Health Programme was estimated at 0.15% total population. CONCLUSIONS/SIGNIFICANCE: The Gambia has reached the elimination threshold for TF in children. Further work is needed to bring the number of unknown TT cases below the elimination threshold

Impact of long-term treatment of onchocerciasis with ivermectin in Kaduna State, Nigeria: first evidence of the potential for elimination in the operational area of the African Programme for Onchocerciasis Control.

BACKGROUND: Onchocerciasis can be effectively controlled as a public health problem by annual mass drug administration of ivermectin, but it was not known if ivermectin treatment in the long term would be able to achieve elimination of onchocerciasis infection and interruption of transmission in endemic areas in Africa. A recent study in Mali and Senegal has provided the first evidence of elimination after 15-17 years of treatment. Following this finding, the African Programme for Onchocerciasis Control (APOC) has started a systematic evaluation of the long-term impact of ivermectin treatment projects and the feasibility of elimination in APOC supported countries. This paper reports the first results for two onchocerciasis foci in Kaduna, Nigeria. METHODS: In 2008, an epidemiological evaluation using skin snip parasitological diagnostic method was carried out in two onchocerciasis foci, in Birnin Gwari Local Government Area (LGA), and in the Kauru and Lere LGAs of Kaduna State, Nigeria. The survey was undertaken in 26 villages and examined 3,703 people above the age of one year. The result was compared with the baseline survey undertaken in 1987. RESULTS: The communities had received 15 to 17 years of ivermectin treatment with more than 75% reported coverage. For each surveyed community, comparable baseline data were available. Before treatment, the community prevalence of O. volvulus microfilaria in the skin ranged from 23.1% to 84.9%, with a median prevalence of 52.0%. After 15 to 17 years of treatment, the prevalence had fallen to 0% in all communities and all 3,703 examined individuals were skin snip negative. CONCLUSIONS: The results of the surveys confirm the finding in Senegal and Mali that ivermectin treatment alone can eliminate onchocerciasis infection and probably disease transmission in endemic foci in Africa. It is the first of such evidence for the APOC operational area

Onchocerciasis in the Americas: from arrival to (near) elimination

Onchocerciasis (river blindness) is a blinding parasitic disease that threatens the health of approximately 120 million people worldwide. While 99% of the population at-risk for infection from onchocerciasis live in Africa, some 500,000 people in the Americas are also threatened by infection. A relatively recent arrival to the western hemisphere, onchocerciasis was brought to the New World through the slave trade and spread through migration. The centuries since its arrival have seen advances in diagnosing, mapping and treating the disease. Once endemic to six countries in the Americas (Brazil, Colombia, Ecuador, Guatemala, Mexico and Venezuela), onchocerciasis is on track for interruption of transmission in the Americas by 2012, in line with Pan American Health Organization resolution CD48.R12. The success of this public health program is due to a robust public-private partnership involving national governments, local communities, donor organizations, intergovernmental bodies, academic institutions, non-profit organizations and the pharmaceutical industry. The lessons learned through the efforts in the Americas are in turn informing the program to control and eliminate onchocerciasis in Africa. However, continued support and investment are needed for program implementation and post-treatment surveillance to protect the gains to-date and ensure complete elimination is achieved and treatment can be safely stopped within all 13 regional foci