Conjunctival Infection Research Articles

Incidence of Bacteria in Conjunctival Infections and their Antibiotic susceptibility

Out of 54 clinical swabs of conjunctivital infections, 24 isolates(44.4%) were identified and tested for their susceptibility to 10 Kinds of antibiotics by disk diffusion method. Beta-lactamase production was done for pencillin resistant Staphylococcus aureus (PRSA).
 The most frequent pathogenes were Staphylococcus aureus (33.3 %), Staphylococcus epidermidis (29.1%), Pseudomonas aeruginosa (16.6%), Streptococcus pneumoniae (12.5)& Haemophilus influenzae (8.3%).20 isolates (83.3 %) showed resistance to pencillin by the disk diffusion method, beta-lactamase production was positive in all (PRSA) isolates. All isolates of S.aureus& S.epidermidis were sensitive to vancomycin (100%).Ciprofloxacin, was the most active antibiotic then gentamycin, chloramphenicol, trimethoprim-sulpham ethoxazole, whereas erythromycin, amoxicillin, tetracyclin and penicillin were the lowest activity.Multiple antibiotic resistance was seen in this study: 2 isolates were resistant to 9 Kinds; 4 isolate was resistant to 8 Kinds; 3isolates were resistant to 7 Kinds ;2 isolates were resistant to 6 Kinds;4 isolates to 5 kinds & 2 isolates to 4 kinds of antibiotics.

Trichiasis Surgery in The Gambia: A 4-Year Prospective Study

Trachoma is the leading infectious cause of blindness. Conjunctival Chlamydia trachomatis infection causes scarring, entropion, trichiasis, and blinding corneal opacification. Worldwide, there are 8 million people with trichiasis. Although trichiasis surgery can reduce the risk of blindness, retrospective data suggest that long-term recurrence rates may be high. A 4-year prospective investigation of recurrent trichiasis was conducted in The Gambia. Patients with trichiasis were examined at baseline, 6 months, 1 year, and 4 years after posterior lamellar tarsal rotation surgery. Conjunctival swabs for bacteriology and PCR for C. trachomatis were collected at baseline, 6 months, and 1 year. Three hundred fifty-six Gambian patients were enrolled at baseline and 266 were reassessed at 4 years (94% of surviving patients). The recurrence rates were 32%, 40%, and 41% at 6 months, 1 year, and 4 years, respectively. At 4 years, 30% of patients had bilateral trichiasis and 21% had bilateral corneal opacity. Recurrence was associated with severe conjunctival inflammation and severe trichiasis (>10 lashes) at baseline. Trichiasis recurrence rates were high, and most cases recurred within 6 months of surgery. The results suggest that there are important aspects of surgical technique and quality that should to be addressed. Persistent inflammation is strongly associated with recurrence at 4 years.

Conjunctival expression of matrix metalloproteinase and proinflammatory cytokine genes after trichiasis surgery.

PURPOSE. Trachoma, the leading infectious cause of blindness, is a chronic inflammatory scarring condition. Blindness follows the development of trichiasis, which is treated surgically. Unfortunately, it frequently recurs, compromising the treatment. In this study, gene expression analysis was used to examine factors that may be involved in the inflammation and tissue remodeling after surgery. METHODS. Subjects were examined before and at 1 and 4 years after surgery. Conjunctival swab samples were collected for bacterial culture, Chlamydia trachomatis PCR, and RNA isolation at 1 year. Quantitative real-time PCR was performed to measure the expression of tumor necrosis factor-alpha (TNF), interleukin-1beta (IL1B), matrix metalloproteinase-1 (MMP1), MMP-2, MMP-9, tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), TIMP-2, and hypoxanthine phosphoribosyl transferase-1 (HPRT1). RESULTS. Two hundred forty individuals with trachomatous trichiasis were recruited. One year after surgery, recurrent trichiasis was associated with a reduced MMP-1/TIMP-1 ratio (P = 0.029). IL1B expression was elevated in the presence of either conjunctival bacterial infection (P = 0.011) or inflammation (P = 0.002). TNF expression was greater in the Mandinka ethnic group (P < 0.0001), and it was increased when clinical inflammation was associated with nonchlamydial bacterial infection (P = 0.012). MMP-9 expression increased when conjunctival inflammation was associated with bacterial infection (P = 0.007). CONCLUSIONS. Recurrent trichiasis was associated with a reduced MMP-1 to TIMP-1 ratio, which may favor the accumulation of fibrotic tissue. Nonchlamydial bacterial infection may induce factors that contribute to conjunctival tissue remodeling and recurrent trichiasis in trachoma. Prospective studies are needed to assess the potential importance of these and other factors in progressive disease.

Diffuse keratoconjunctival diseases: an in vivo confocal microscopic study

Abstract Purpose To establish in vivo confocal microscopic features of diffuse ocular surface disease. Methods IVCM of diffuse OSD such as chemical burns, inflammatory disease related limbal stem cell deficiency, conjunctival intraepithelial neoplasia and OS infections was carried out using the Rostock Cornea Module RCM and HRTII. In some patients subsequent biopsy or surgery allowed for histological correlation of the observed IVCM features. Results Multiple clinical and histological correlations have enabled us to establish diagnostic features of dendritic cells, inflammatory cells, metaplastic and dysplastic superficial and basal epithelial cells, goblet cells, intraepithelial cysts, corneal new vessels, subtypes of acanthamoeba cysts and other nonspecific features. These features can be seen individually or in combination in different diseases entities. Conclusion IVCM can help in making rapid clinical diagnoses without resort to biopsy or impression cytology. This in turn allows for early initiation of appropriate treatment. Commercial interest

The Enigma of Galileo's Eyesight: Some Novel Observations on Galileo Galilei's Vision and His Progression to Blindness

Galileo Galilei became blind. Before this happened he revealed that his left eye had always had less than perfect vision. A study of his written works, his handwriting, and the originals of the portraits undertaken during his lifetime indicate that this probably was the case. These portraits suggest that his left eye tended to lose fixation and that, at the age of 60, he suffered from a mucocoele of the right frontal sinus; but these conditions would not have caused blindness. Considering the systemic diseases from which he suffered over his lifetime, he could possibly have had a long standing uveitis with secondary pupillary block glaucoma, common in those with the group of conditions classified as sero-negative arthropathies. Posterior scleritis with secondary glaucoma is less likely. If either of these were the cause, then the disease was probably triggered by a well-documented, severe acute illness as a young adult, the inflammation being localized to the eye as a result of severe recurrent conjunctival infections in his youth. The intermittent nature of the visual loss, the normal appearance of the cornea and pupils in his portraits, the absence of any evidence of inflammatory joint disease, the presence of halos, and the severe nature of the pain—combined with the high level of visual acuity in between attacks and its persistence until the last few weeks of vision means that angle-closure glaucoma must also be considered. These suggestions might be confirmed or refuted by studying his remains. Application has been made for this to be done.

The emergence of lymphogranuloma venereum in Europe

A 42-year-old white homosexual man presented to our clinic in April, 2008, with a 12-day history of right knee and back pain, conjunctivitis, and proctitis. 10 days earlier, after a normal radiograph, an arthrocentesis of his right knee had been done; 40 mL of clear synovial fl uid was aspirated and corticosteroids were injected locally. There was no history of recent injury, febrile illness, or rheumatological conditions. He reported anonymous unprotected receptive anal sex 1 month earlier. Since 2000, he had had three episodes of uncomplicated urethritis, secondary syphilis, HIV, and an episode of primary syphilis (rapid plasma reagin [RPR] 1/32 in August, 2007). He had been taking antiretrovirals since October, 2007, with a CD4 count of 300 per μL (31%) and undetectable viral load in March, 2008. On examination, his right knee was cool, swollen, and painful, and he had a right non-purulent conjunctivitis. Proctoscopy showed a hyperaemic mucosa with superfi cial ulcers and a mucopurulent exudate (fi gure A); gram stain showed more than 40 leucocytes per high-power fi eld (magnifi cation ×1000) without diplococci. Making a presumptive diagnosis of lymphogranuloma venereum and sexually acquired reactive arthritis (SARA), we gave our patient 100 mg doxycycline twice daily for 21 days and non-steroidal anti-infl ammatory drugs (NSAIDs). He returned 4 days later because of diffi culty walking (he was using crutches), fever (38·5°C), and a painful and swollen right elbow and left knee (fi gure B). Arthrocentesis of his left knee was done and 45 mL of synovial fl uid was aspirated. Laboratory test results showed RPR 1/8 and TPHA 1/2560; rectal and conjunctival infection with Neisseria gonorrhoeae and conjunctival infection with chlamydia were ruled out. Rectal lymphogranuloma venereum was diagnosed using real-time PCR. On day 10 his general condition improved, he had no fever or conjunctivitis, and proctitis was improving, although he was still using crutches. Cultures from synovial fl uid were negative, haematological and other blood tests were normal, HLA-B27 was negative, although C-reactive protein was mildly raised at 13·79 mg/L. On day 12, he had another arthrocentesis of his right knee with aspiration of 112 mL of serous fl uid, and he was prescribed prednisone 5 mg three times daily. By day 39, on tapered prednisone, he felt “80%” better and proctoscopy showed no rectal infl ammation. PCR for the lymphogranuloma venereum-causing organism was negative on day 46. When last seen in August, 2008, the patient was well. SARA is a spondyloarthritis and an important cause of lower limb oligoarthritis, predominantly aff ecting young adults. It consists of sterile axial or peripheral articular infl ammation, enthesitis, and extra-articular manifestations. Reactive arthritis is precipitated by an infection localised in the genitourinary or gastrointestinal tract and susceptibility may be related with the HLA-B27 gene. The bacteria principally involved are chlamydia, salmonella, shigella, campylobacter, and yersinia species. Diagnosis is a two-stage process requiring demonstration of a temporal link with a recognised trigger infection. The standard therapy is NSAIDs and steroids. Lymphogranuloma venereum is a systemic sexually transmitted infection caused by the L serovars of Chlamydia trachomatis. Since 2003, outbreaks of rectal lymphogranuloma venereum have occurred in Europe aff ecting mostly core groups of HIV-positive homosexual men, although arthritis rarely accompanies infection. We have diagnosed 35 cases of lymphogranuloma venereum as of October, 2008. Lymphogranuloma venereum in Europe is unknown by many physicians not working in genitourinary medicine and is frequently diagnosed late in patients with proctitis. Therefore, because of increasing cases, physicians should be aware that lymphogranuloma venereum can also be a cause of SARA.

The Development of an Age-Structured Model for Trachoma Transmission Dynamics, Pathogenesis and Control

BackgroundTrachoma, the worldwide leading infectious cause of blindness, is due to repeated conjunctival infection with Chlamydia trachomatis. The effects of control interventions on population levels of infection and active disease can be promptly measured, but the effects on severe ocular sequelae require long-term monitoring. We present an age-structured mathematical model of trachoma transmission and disease to predict the impact of interventions on the prevalence of blinding trachoma.Methodology/Principal FindingsThe model is based on the concept of multiple reinfections leading to progressive conjunctival scarring, trichiasis, corneal opacity and blindness. It also includes aspects of trachoma natural history, such as an increasing rate of recovery from infection and a decreasing chlamydial load with subsequent infections that depend upon a (presumed) acquired immunity that clears infection with age more rapidly. Parameters were estimated using maximum likelihood by fitting the model to pre-control infection prevalence data from hypo-, meso- and hyperendemic communities from The Gambia and Tanzania. The model reproduces key features of trachoma epidemiology: 1) the age-profile of infection prevalence, which increases to a peak at very young ages and declines at older ages; 2) a shift in this prevalence peak, toward younger ages in higher force of infection environments; 3) a raised overall profile of infection prevalence with higher force of infection; and 4) a rising profile, with age, of the prevalence of the ensuing severe sequelae (trachomatous scarring, trichiasis), as well as estimates of the number of infections that need to occur before these sequelae appear.Conclusions/SignificanceWe present a framework that is sufficiently comprehensive to examine the outcomes of the A (antibiotic) component of the SAFE strategy on disease. The suitability of the model for representing population-level patterns of infection and disease sequelae is discussed in view of the individual processes leading to these patterns.

Infectious agents and lymphoma development: molecular and clinical aspects

This review is focused on the role of infectious agents in the development of some lymphoma entities. Associations involving bacterial infections mostly regard marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT)-type. Some paradigmatic examples of these associations include the Helicobacter pylori-related gastric MALT lymphoma and the more recently reported links between Chlamydophila psittaci and ocular adnexal MALT lymphomas and Borrelia burgdorferi and cutaneous MALT lymphomas. The well-documented association between Epstein-Barr virus infection and related lymphoproliferative disorders are analysed as an example of lymphotropic virus with tumourigenic activity. Molecular, biological and clinical features as well as therapeutic implications of these associations are analysed and future perspectives in this field are discussed.

Effect of Chlamydiaphage φCPG1 on the Course of Conjunctival Infection with “ Chlamydia caviae ” in Guinea Pigs

Over the last several years, four different phages of chlamydiae, in addition to a phage associated with Chlamydia psittaci isolated from an ornithosis infection in ducks over 25 years ago, have been described and characterized. While these phages and their chlamydial host specificities have been characterized in vitro, there is virtually nothing known about the interaction of the phage with chlamydiae in their natural animal host. phiCPG1 is a lytic phage specific for "Chlamydia caviae," which is a natural parasite of the guinea pig. In this study, guinea pigs were inoculated in the conjunctiva with suspensions of phiCPG1 and C. caviae and the effect on the development of pathology and on the course of chlamydial infection in the conjunctiva was determined. The presence of phage delayed the appearance of the peak level of chlamydiae in the animal and decreased the pathological response. Evidence for replication of the phage in C. caviae in the conjunctival tissue was observed. Modifying the ratio of phage to chlamydiae altered the course of infection and affected phage replication. There was no evidence for the phage increasing the virulence of C. caviae infection.

Les fluoroquinolones en ophtalmologie : indications et modalités d’utilisation

Fluoroquinolones are commonly used in ophthalmology, either for conjunctival infections or endophthalmitis. Use of these antibiotics requires good knowledge of the pharmacokinetic profile and adverse effects, and contraindications must be respected. Fluoroquinolones are useful in 2008 given their antibacterial spectrum, good ocular penetration, and the potential benefit of intravitreal injection.

Antibiotic fusidic acid has strong interactions with negatively charged lipid membranes: An electrokinetic capillary chromatographic study

Fusidic acid (FA), a narrow spectrum steroidal antibiotic, is useful for treatment of most skin, conjunctival, and corneal infections and also in infections caused by atypical microbes in the surface of the eye. Liposome electrokinetic capillary chromatography (LEKC) was used to study the interactions between FA and lipid membranes. Liposomes prepared by extrusion were composed of 1-palmitoyl-2-oleyl- sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleyl- sn-glysero-3-phosphor- l-serine (POPS), cholesterol, FA, and sphingomyelin (SM) in various molar ratios. 26 different liposome dispersions were studied as dispersed (pseudostationary) phase in LEKC. The hydrophobicities of the liposomes were evaluated by calculating the retention factors of model neutral steroids. The retention factors were calculated using the EOF and the effective electrophoretic mobilities of the analytes and the liposomes. The latter were separately determined by capillary electrophoresis with a polyacrylamide (PAA)-coated capillary. FA–lipid membrane interactions were studied by determining the retention factor of FA. In addition, liposomes prepared from lipids extracted from Escherichia coli bacterium were studied and used as dispersed phase in LEKC for interaction studies between FA and lipid membranes.

The Possibility of Human Adenovirus Detection From the Conjunctiva in Asymptomatic Cases During Nosocomial Infection

To prevent outbreaks of nosocomial adenoviral conjunctivitis, proper management for transmission control must be performed. We collected conjunctival samples from asymptomatic inpatients and an ophthalmologist in an ophthalmology ward and attempted to detect the human adenovirus (HAdV) pathogen for infection control. One inpatient was diagnosed with adenoviral conjunctivitis on the basis of typical, acute, and severe symptoms and virologic testing by using an immunochromatography (IC) kit. To survey nosocomial infection, conjunctival swabs from 17 other inpatients and 1 ophthalmologist without obvious symptoms of adenoviral conjunctivitis were sampled and analyzed for HAdV pathogens with an IC kit, viral isolation, nested polymerase chain reaction (PCR), and real-time PCR. HAdV antigens and DNA were detected from 1 and 8 of the 18 samples collected for nosocomial survey by IC kit and nested PCR method, respectively. Moreover, infectious HAdV was isolated in the cell culture from only 1 antigen-positive sample. All PCR-positive samples had identical nucleotide sequences of the partial hexon gene and were determined to be HAdV type 37 by phylogenetic analysis. No inpatients tested showed any symptoms of typical adenoviral conjunctivitis, but slight conjunctival infection caused by postoperative reaction and/or mild conjunctivitis that did not resemble HAdV infection was observed. No one developed typical adenoviral conjunctivitis over the 2-month follow-up. The clinical course of adenoviral conjunctivitis varies from inapparent infection to severe conjunctivitis. Mild or inapparent HAdV conjunctival infection could be common during conjunctivitis outbreaks and might play a role in the spread of nosocomial adenoviral conjunctivitis.

Normal Conjunctival Flora

Objective: To determine the prevalence of normal conjunctival flora and its types. Study Design: An observational study. Place And Duration of Study: At Ophtha-lmological Department, DHQ/Allied Hospital, PMC, Faisalabad, from November 2006 to February 2007. Patients And Methods: This study was performed on 500 patients, aged form 20 years to 70 years with normal looking eyes. The samples of sterile stuart’s swab were made on conjunctiva of patients, without touching eyelashes or lid margins. The swabs were touched with conjunctiva of both eyes and placed in stuart’s transparent media to shift to microbiological laboratory. Results: Out of 500 swabs 412 (82.4%) showed no growth while 78 (15.6%) showed microbial growth. Out of these 78 swabs, there were 44 (56.41%) having normal flora, while 34 (43.59%) had other pathogens. Conclusion: The normal looking eyes harbour different types of the organisms. Any trauma, accidental hurt or elective surgical procedure is not free from risk of conjunctival infection, keratits or endophthalmitis etc.

A truvada hypersensitivity reaction simulating abacavir hypersensitivity

Hypersensitivity reactions to abacavir occur in approximately 5% of treated individuals, and may be manifested by fever, rash, constitutional complaints, gastrointestinal disturbances and hematological abnormalities [1]. These reactions can be life-threatening particularly if patients are re-challenged with abacavir [2]. The presence of HLA-B*5701 has been associated with a higher risk of abacavir hypersensitivity reactions in Caucasian and Hispanic populations [3,4]. To date, no other nucleoside reverse transcriptase inhibitors have been reported to cause similar hypersensitivity reactions. We report a case of an emtricitabine/tenofovir hypersensitivity reaction. An 18-year-old African American man with a CD4 cell count of 322 cells/μl and an HIV-1-RNA viral load of 4550 copies/ml was admitted to the hospital with a 2-day history of fevers to 103.6°F, fatigue, myalgias, conjunctival infection and non-bloody diarrhea. He denied nausea or vomiting but had a poor appetite over this time. Ten days previously, he had entered a randomized clinical trial for antiretroviral-naive patients. He initiated open-label treatment efavirenz and blinded treatment with emtricitabine/tenofovir (or placebo) or abacavir/lamivudine (or placebo). The patient's physical examination revealed a temperature of 102.2°F and orthostatic hypotension. His laboratory findings were significant for an elevated white blood cell count of 17 000 cells/μl, blood urea nitrogen level of 23 mg/dl, and creatinine level of 1.4 mg/dl. Intravenous fluids and broad-spectrum antibiotics were administered. HIV medications were withheld. Blood, urine and stool cultures were negative, and a computed tomography scan of the abdomen and pelvis was normal. The patient recovered and went home after 4 days with suspected bacterial gastroenteritis on ciprofloxacin and metronidazole. The patient returned to the study unit the day after discharge and received his study medications under direct observation. Within one hour, he complained of a headache and numbness of his hands and feet. He then had projectile vomiting and was subsequently found to have a systolic blood pressure of 70 mmHg and a heart rate of 140 beats a minute. Physical examination showed early desquamation of his scalp and face. The patient was transferred to the medical intensive care unit where he received intravenous fluids and brief hemodynamic support with vasopressors. All cultures remained negative. HIV medications were withheld, and he recovered after 4 days. The patient was diagnosed clinically with an abacavir hypersensitivity reaction. The unblinding process revealed that he had been randomly selected to receive emtricitabine/tenofovir. Mass spectroscopy of the dispensed medications confirmed that the patient's pills indeed contained emtricitabine/tenofovir. The patient was subsequently given zidovudine/lamivudine and efavirenz without further problems. Abacavir hypersensitivity is a potentially fatal syndrome with a multisystemic presentation [1]. Our patient presented within 10 days of initiation of his medications and exhibited many features similar to those reported with abacavir hypersensitivity, including fever, myalgias, fatigue, diarrhea, rash and hypotension. His symptoms resolved rapidly after discontinuing the medications and became much more severe upon rechallenge. The initial assessment by the caring physicians was that he had an acute febrile illness, probably viral or bacterial in origin, and that it would be safe to resume his antiretroviral therapy. We believe this is one of the first reports of a systemic emtricitabine/tenofovir hypersensitivity reaction. We cannot discern which drug might have induced this reaction. The patient was successfully given lamivudine subsequently, which is chemically similar to emtricitabine [5]. In a recent research letter, Lockhart described nine patients with suspected tenofovir cutaneous hypersensitivity reactions, all manifesting as maculopapular or vesicular rashes [6]. Only one of their patients appeared to have a more systemic illness that included urticaria, shortness of breath, and angioedema. Our patient did not present with either a maculopapular or vesicular rash, but did have desquamation of his scalp and face. He had more of a systemic illness that involved gastrointestinal symptoms, fever, and hypotension, similar to the reaction seen with abacavir hypersensitivity. We thus suspect that this patient had a systemic reaction to tenofovir. Clinicians should consider hypersensitivity reactions in patients taking nucleoside or nucleotide reverse transcriptase inhibitors who present with a systemic illness. Hypersensitivity reactions similar to those described with abacavir may occur with other nucleoside reverse transcriptase inhibitors. It may be prudent to hold these medications upon presentation and exercise caution with rechallenge. Sponsorship: This work was supported by ACTG training grant U01069513-01. Conflicts of interest: C.J.F. has received honoraria and research grants from Gilead Sciences, Inc.

Prevention of Vaccinia Infection in a Laboratory Worker

Because smallpox may be a weapon, immunization programs have been restarted and research continues with vaccinia (smallpox vaccine). Ocular complications occur in 5 to 9% of those who contract smallpox and in 10 to 20 per million vaccinia recipients through self-inoculation or from contact with vaccinated individuals. Both variola virus (smallpox) and vaccinia virus (smallpox vaccine) are orthopoxviruses that can cause conjunctival and eyelid infections, cornea ulceration, keratitis, iritis, optic neuritis, and loss of vision. Clinicians should maintain a high index of suspicion for smallpox vaccine-associated reactions in vaccinia researchers, the immunized, and their close contacts. A researcher sprayed vaccinia in her eye. Timely irrigation may have prevented a viral infection. The possibility that this individual had self-immunized herself with smallpox vaccine via the conjunctiva and preventive measures are discussed. Greater precautionary measures need to be taken to prevent laboratory accidents. Antiviral ophthalmic medication and vaccinia-immune globulin medication are treatment options.

Traction sutures for exotropia in longstanding third nerve palsy

Background: Exotropia in longstanding third nerve palsy presents a significant cosmetic problem and the management is difficult. Methods: A retrospective review of patients with longstanding exotropia secondary to third nerve palsy between 1996 and 2006 was carried out. Patients underwent large lateral rectus recession and medial rectus resection, combined with muscle traction sutures. Traction sutures were passed through superior and inferior rectus insertions and through the fornix to the medial canthus; the eye was adducted and sutures were brought through the lid to the skin surface and tied over bolsters. Traction sutures were left in situ for 6 weeks. Results: Thirty-three patients were treated, with a mean follow up of 16 months (range, 3-108 months). The age range was 3 to 66 years (mean, 28.8). The cause of third nerve palsy was congenital in 39%; orbital or intracranial tumor in 21%; traumatic in 15%; microvascular in 9%; complication of neurosurgery in 9%; and unknown in 6%. Prism cover test (PCT) measurements ranged from 25Δ to 95Δ exotropia preoperatively (mean, 60Δ exotropia). After removal of the traction sutures, the eye maintained a good cosmetic position in all but three cases. Final PCT ranged from 16Δ esotropia to 40Δ exotropia (mean, 14.5Δ exotropia). Postoperative motility was extremely limited. Very limited abduction was a good indicator of the final eye position. Complications included conjunctival hypertrophy, suture infection, and cheese wiring. Conclusions: Adducting traction sutures combined with large recess-resect of the horizontal recti are safe and effective in the management of longstanding strabismus in third nerve palsy.

Pradofloxacin release from the OphthaCoil: a new device for sustained delivery of drugs to the eye

The release of the antibiotic pradofloxacin from a new ocular insert called the OphthaCoil was evaluated. The ocular insert consists of a drug-loaded adherent hydrogel on a thin wire, which is coiled. The inner lumen of the coil was filled with a polymer rod made from a poly(2-hydroxyethyl methacrylate) hydrogel and loaded with the same drug. The in vitro release of pradofloxacin and its pharmacokinetics in dog tear fluid was evaluated over a 72-h time interval. The results show that in vitro release is faster than in vivo release, probably because the refresh time for tear fluid in the eye is slower than in the in vitro experiments. In vivo, the drug level in the tear fluid remained within the concentration range during the entire 72 h, which is when pradofloxacin is expected to be active against the most relevant bacteria species involved in canine conjunctival infections. These results are quite promising for the future application of the OphthaCoil in veterinary or human ophthalmology.

Differential expression of homing receptors and vascular addressins in tonsils and draining lymph nodes: Effect of Brucella infection in sheep

The differential expression of homing receptors (HR) and complementary vascular addressins was studied in T and B lymphocytes from ovine tonsils and draining lymph nodes (LN) in uninfected and Brucella melitensis-infected sheep. In uninfected sheep, CD4 +CD25 + T cells expressed proportionally more L-selectin and β1 integrin than β7 integrin in pharyngeal and palatine tonsils and in parotid LN (PLN), retropharyngeal LN (RLN) and the peripheral prescapular LN (PSLN). In contrast, memory CD4 +CD45RA − T cells expressed an equivalent proportion of the three HR in PLN and PSLN, whereas β1 and β7 integrins were proportionally more expressed than L-selectin in pharyngeal tonsil. β7 integrin was proportionally more expressed than β1 integrin or L-selectin in palatine tonsils, RLN and the mucosal mesenteric LN (MLN). β1 integrin was proportionally more expressed in IgG + and IgA + cells than β7 integrin and L-selectin in tonsils, PLN and RLN. The main endothelial addressin expressed on venules in both pharyngeal and palatine tonsils, the PLN and RLN, as well as in the PSLN, was the peripheral PNAd, while in the MLN it was MAdCAM-1. Conjunctival infection by Brucella resulted in an increase of CD4 +CD25 + and CD4 +CD45RA − T cell subsets, which was associated to modifications of HR expression. CD4 +CD45RA − T cells expressed proportionally more β1 and β7 integrins than L-selectin in regional PLN and RLN, but also in PSLN. The infection induced an increase of IgG + and IgA + cell percentages expressing β1 integrin in all LN, and also β7 integrin in the RLN. PNAd continued to be expressed on venules of tonsils and draining LN after Brucella infection, and MAdCAM-1 was also weakly expressed on RLN venules. These results suggest that lymphocyte trafficking through tonsils and draining LN could involve L-selectin/PNAd interactions, as well as β1 or β7 integrin, possibly in interaction with VCAM-1 or MAdCAM-1. The homing of antigen-specific lymphocytes in these tissues could be modulated after conjunctival infection with Brucella, which induces the recruitment of lymphocytes that express both β1 and/or β7 integrin in regional and more distant LN.

Conjunctival FOXP3 Expression in Trachoma: Do Regulatory T Cells Have a Role in Human Ocular Chlamydia trachomatis Infection?

BackgroundTrachoma, caused by ocular infection with Chlamydia trachomatis, remains the leading infectious cause of blindness and in 2002 was responsible for 3.6% of total global blindness. Although transmission can be successfully interrupted using antibiotics and improvements in public and personal hygiene, the long-term success of the control programmes advocated by the World Health Organization are still uncertain. For the complete control and prevention of trachoma, a vaccine would be highly desirable. Currently there are no licensed vaccines for trachoma, and no human vaccine trials have been conducted since the 1960s. A barrier to new attempts to design and introduce a vaccine is the identification of immunologic correlates of protective immunity or immunopathology. We studied important correlates of the immune response in a trachoma-endemic population in order to improve our knowledge of this disease. This is essential for the successful development of a vaccine against both ocular and genital C. trachomatis infection.Methods and FindingsWe used quantitative real-time PCR for C. trachomatis 16S rRNA to identify conjunctival infection. The expression of IFN-γ, IDO, IL-10, and FOXP3 mRNA transcripts was measured. We evaluated the role of immune effector and regulatory responses in the control of chlamydial infection and in the resolution of clinical signs of trachoma in endemic communities in Gambia. All host transcripts examined were detectable even in normal conjunctiva. The levels of these transcripts were increased, compared to normal uninfected conjunctiva, when infection was detected, with or without clinical disease signs. Interestingly, when clinical disease signs were present in the absence of infection, the expression of a regulatory T cell transcription factor, FOXP3, remained elevated.ConclusionsThere is evidence of an increase in the magnitude of the local anti-chlamydial cytokine immune responses with age. This increase is coupled to a decline in the prevalence of infection and active trachoma, suggesting that effective adaptive immunity is acquired over a number of years. The anti-chlamydial and inflammatory immune response at the conjunctival surface, which may control chlamydial replication, is closely matched by counter inflammatory or regulatory IL-10 expression. Differences in the level of FOXP3 expression in the conjunctiva may indicate a role for regulatory T cells in the resolution of the conjunctival immune response, which is important in protection from immunopathology. However, the expression of cytokines that control chlamydial replication and those that regulate the conjunctival immune response is not simply juxtaposed; the interaction between the infection and the clinical disease process is therefore more complex.

Efficacy of topical cobalt chelate CTC-96 against adenovirus in a cell culture model and against adenovirus keratoconjunctivitis in a rabbit model.

BackgroundAdenovirus (Ad), associated with significant morbidity, has no topical treatment. A leading CTC compound (CTC-96), a CoIII chelate, was found to have potent in vitro and in vivo antiviral efficacy against herpes viruses. In this study CTC-96 is being tested for possible anti-Adenovirus activity.MethodsThe biological anti-adenovirus activity of CTC-96 in concentrations from 5 to 250 ug/ml, was evaluated initially by viral inactivation (viral exposure to CTC-96 followed by dilution and inoculation of cells), virucidal (viral exposure to CTC-96 and inoculation of cells without dilution) and antiviral (effect of CTC-96 on previously adsorbed virus) plaque assays on HeLa (human cervical carcinoma), A549 (human lung carcinoma) and SIRC (rabbit corneal) cells. After verifying the antiviral activity, New Zealand White rabbits were infected with Ad-5 into: 1) the anterior cul-de-sac scarifying the conjunctiva (Group "C+"); 2) the anterior cul-de-sac scarifying the conjunctiva and cornea (Group "CC+"); 3) the stroma (Group "CI+"). Controls were sham-infected ("C-", "CC-", "CI-"). Other rabbits, after "CC", were treated for 21 days with: 1) placebo, 9x/day ("-"); 2) CTC-96, 50 ug/ml, 9x/day ("50/9"); CTC-96, 50 ug/ml, 6x/day ("50/6"); CTC-96, 25 ug/ml, 6x/day ("25/6"). All animals were monitored via examination and plaque assays.ResultsIn vitro viral inactivation, virucidal and antiviral assays all demonstrated CTC-96 to be effective against Adenvirus type 5 (ad-5). The in vivo model of Ad keratoconjunctivitis most similar to human disease and producing highest viral yield was "CC". All eyes (6/6) developed acute conjunctivitis. "CI" yielded more stromal involvement (1/6) and iritis (5/6), but lower clinical scores (area × severity). Infection via "C" was inconsistent (4/6). Fifty (50) ug/ml was effective against Ad-5 at 6x, 9x dosings while 25 ug/ml (6x) was only marginally effective.ConclusionCTC-96 demonstrated virucidal activity against Ad5 in tissue culture with HeLa, A549 and SIRC cell lines.Animal Model Development: 1) "CC" produced conjunctival infection with occasional keratitis similar to human disease; "CI" yielded primarily stromal involvement; 2) "C" consistently produced neither conjunctivitis nor keratitis.CTC Testing: 1) Conjunctivitis in all eyes; 2) Resolution fastest in "50/9" ("50/9". "50/6" > "25/6" > "-"); 3) Efficacy in "50/6" was not statistically different than "50/9"; 4) Conjunctival severity was lower in treatment groups then controls; 5) Little corneal or intra-ocular changes were noted.