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Biomedical subjects

N Morlet

Publications and source records attributed to N Morlet.

At least 19 recordsLinked to original sources
PubMed1999

Etoposide as a virocidal anticytomegalovirus therapy: intravitreal toxicology and pharmacology in rabbits.

BACKGROUND: Although Cytomegalovirus (CMV) retinitis is now a common intraocular infection, current therapy is only virostatic so ongoing treatment is required. Etoposide was found to be virocidal for CMV in laboratory experiments and it might prove to be beneficial clinically. We investigated the toxicity and intraocular concentration of etoposide (VP16) and its new analogue etoposide-phosphate (VP16P) following intravitreal injections in rabbit eyes. METHODS: First a sequential dose-response was assessed with flash electroretinogram for both eyes of light- and dark-adapted rabbits (n = 7; one rabbit for each dose) over a range of light intensities before and after intravitreal injection of VP16 or VP16P to one eye; the other eye was injected with normal saline as a control. A multidose study was then performed on four rabbits. A non-toxic dose of VP16P (50 or 75 g) was injected into the vitreous of one eye on four occasions 1 week apart. A photopic electroretinogram was performed before the first injection and 6 weeks after the last injection. All the eyes from the electroretinogram studies were fixed in formalin, placed in paraffin, then stained with haematoxylin and eosin and examined under a light microscope. To determine the time-course of the intraocular concentrations of VP16P a sequential pharmacokinetic study was performed using a further 12 rabbits. Each rabbit was injected with 50 g VP16P to one eye and 75 g VP16P to the other eye. Three of these rabbits were killed at 1, 3, 6 and 9 h after injection. Samples of vitreous were assayed for both VP16 and VP16P using HPLC. An in vitro dose response assay was performed using third-passage bovine retinal pigment epithelial (RPE) cells cultured in Dulbecco's modified Eagles medium with fetal calf serum. The effect of a log-dose increment of VP16P on the RPE cell proliferation was assessed using tritiated thymidine incorporation. RESULTS: The electroretinogram studies suggested that VP16 was toxic even with the 10 g dose. For VP16P a toxic effect was noted following injection of a single dose greater than 100 g. Multiple injections of 50 or 75 g VP16P did not produce a toxic response. Histological examination demonstrated significant abnormality only with the 500 g dose of VP16 or VP16P. VP16P was rapidly metabolized to VP16 in the eye, producing concentrations of 2.0 g/mL or more for up to 9 h following a 75-microg dose. This suggests that the electroretinogram findings following VP16 injections were confounded by a toxic effect of the ethanol solvent (which is absent from the VP16P preparation). VP16P was quite potent, the ID50 was about 0.1 g/mL for bovine RPE cells in the in vitro assay. DISCUSSION: These results indicate that multiple 75-gVP16P intravitreal injections were not toxic to the rabbit eye and provide a therapeutic intraocular concentration for up to 9 h after the injection.

Animals↗
PubMed1999

Biofilm on scleral explants with and without clinical infection.

PURPOSE: Biofilm is a glycocalyx matrix secreted by microorganisms that confers protection against host defenses and antimicrobial treatment. Biofilms have been implicated in the persistence of scleral buckle infections. This study aimed to evaluate the incidence of biofilm growth on scleral explants and the relationship to explant infection. METHODS: Scleral explants were obtained following removal for infection or extrusion or during repeat surgery. Explants were fixed with rhuthenium red and examined by scanning electron microscopy to visualize the glycocalyx. RESULTS: A total of 28 explants were analyzed. Ten were removed because of either infection or extrusion and 18 were removed during repeat surgery. The mean time to removal of explants was 36 months in the infection/extrusion group and 12 months in the others. Biofilm was identified on five explants-two removed because of infection/extrusion and three for surgical indications. Bacterial elements were identified in all biofilms. CONCLUSIONS: Biofilm was identified on explants removed because of infection or exposure and on explants removed for technical reasons at repeat surgery. This implies that bacterial contamination and biofilm formation occur without exposure of the explant, probably due to inoculation at the time of initial surgery. Biofilms may contribute to the persistence of scleral explant infections but a causative role in buckle extrusion is unproved.

Biofilms↗
PubMed1999

Risk factors for treatment outcome of suspected microbial keratitis. Ofloxacin Study Group.

BACKGROUND: Primary treatment for suspected microbial keratitis is generally successful. Although risks such as contact lens use are well recognised as causative factors for microbial keratitis, little is known about the risk factors that influence treatment outcome. The present study evaluates the risk factors assessed at diagnosis as prognostic indicators of primary treatment failure. METHODS: Patients were prospectively enrolled in the ofloxacin treatment trial and data concerning symptoms, treatments, past and concurrent eye disease were collected along with the measurement of corneal ulcer size at the slit lamp. All patients were scraped for microbiological investigation, and treated with either ofloxacin (0. 3%) or standard therapy of fortified cefuroxime and gentamicin drops. Treatment success was complete healing of the ulcer with zero dimensions of the epithelial defect within 2 weeks of start of treatment. The important prognostic indicators were selected by comparison among those who failed treatment, had delayed healing, or were culture positive with other patients using univariate and stratified analysis. These were then used in a Poisson model for multiple regression analysis to estimate the relative risk of the main prognostic variables. RESULTS: Of the 118 patients enrolled in the study, 14 were identified as primary treatment failures, 17 had slow healing, and 15 indolent ulcers. There were 49 culture positive patients. The multivariate analysis identified that large culture positive ulcers in patients 60 years or older had 5.5 times the risk of primary treatment failure (p<0.001). Significant predictors of slow healing were previous ocular disease and a positive culture; significant predictors of indolent ulceration were previous ocular disease and steroid use at diagnosis; the main predictor of a culture positive result was ulcer size. CONCLUSIONS: Elderly patients with large ulcers were more likely to be culture positive, fail primary therapy, and require surgical intervention. A positive microbial culture provided prognostic information regardless of the organism isolated. However, this information was of less value for those with small ulcers and for younger patients.

Adolescent↗
PubMed1998

High-dose (2000-microgram) intravitreous ganciclovir in the treatment of cytomegalovirus retinitis.

OBJECTIVE: The authors prospectively studied visual outcome, relapse, complications, and survival of patients with acquired immune deficiency syndrome (AIDS)-related cytomegalovirus (CMV) treated with high-dose intravitreous ganciclovir (2 mg/0.1 ml) injections. The outcomes were compared with those of patients treated with standard doses of intravenous ganciclovir in the same institution. The histopathologic and electrophysiologic effects of high-dose intravitreous ganciclovir injections in rabbits also were studied. DESIGN: A nonrandomized case series. PARTICIPANTS: A total of 42 patients (74 eyes) were treated with intravitreous injections and 18 patients (27 eyes) were treated with intravenous ganciclovir. Five eyes of three New Zealand white rabbits were injected with ganciclovir, and the sixth eye was a control specimen. INTERVENTION: Patients treated with intravitreous injections received twice-weekly doses of 2 mg/0.1 ml ganciclovir for 3 weeks, then weekly injections. Patients treated with intravenous ganciclovir received standard doses. Patients were monitored with regular examinations. Rabbit eyes were given intravitreous injections of 1 mg/0.1 ml of ganciclovir weekly for 4 weeks. MAIN OUTCOME MEASURES: Assessments of vision, retinal inflammation, and survival were made. Electroretinograms were performed on the rabbit eyes, and they were processed for light and electron microscopy. RESULTS: In the intravitreous group, visual acuity (VA) was stable in 64 of 74 eyes, 5 improved, and 5 deteriorated. Sixty-three (85%) of 74 eyes had final VA of 20/20 to 20/40. Relapse occurred in five eyes (7%; median time, 42 weeks). There were three cases of endophthalmitis. Median survival after diagnosis of CMV retinitis was 36 weeks. In the intravenous group, VA was stable in 18 eyes, 0 improved, and 9 deteriorated. Sixteen (59%) of 27 eyes had final VA of 20/20 to 20/40. Relapse occurred in 15 eyes (56%) at a median time of 21 weeks. Median survival was 21 weeks. The rabbit studies showed no evidence of toxicity. CONCLUSION: High-dose intravitreous ganciclovir effectively suppressed CMV retinitis, preserved vision, and prevented relapse without deterioration in survival.

AIDS-Related Opportunistic Infections↗
PubMed1998

The systemic absorption of adrenaline from posterior segment infusion during vitreoretinal surgery.

BACKGROUND/PURPOSE: Adrenaline infused into the posterior segment of the eye during vitreoretinal surgery may be absorbed and give rise to unwanted cardiovascular effects. We sought to establish whether significant amounts of adrenaline are systematically absorbed. METHODS: This study was prospective and double-masked, with patients randomised into two groups. The first group received a posterior segment infusion containing Hartmann's solution alone (Hs group) and the second group received a posterior segment infusion of Hartmann's solution containing 0.5 ml of 1:1000 (0.5 mg) adrenaline per 500 ml (Hs + Ad group). Pre-medication and anaesthetic techniques were standardised for all patients. Venous blood samples were collected prior to induction, 5 min following intubation and 5, 10, 15 and 30 min following the commencement of the infusion. Samples were analysed for adrenaline levels using high-performance liquid chromatography. RESULTS: Ten patients were studied: 4 in the Hs group and 6 in the Hs + Ad group. The mean dose of adrenaline administered in the Hs + Ad group was 655.08 nmol (0.12 mg). The median serum adrenaline level following infusion for the Hs + Ad group was 0.15 nmol/l (LQ = 0.100, UQ = 0.360) and the median serum adrenaline level for the Hs group was 0.10 nmol/l (LQ = 0.100, UQ = 0.350). There was no overall statistical difference in the levels of serum adrenaline between the two groups, and furthermore adrenaline levels remained within physiological parameters for both groups. CONCLUSION: There does not appear to be significant adrenaline absorption from posterior segment infusion. Continued caution should be exercised, however, as idiosyncratic reactions may still occur.

Absorption↗
PubMed1998

Patterns of peri-operative prophylaxis for cataract surgery: a survey of Australian ophthalmologists.

BACKGROUND: Although peri-operative prophylaxis to prevent endophthalmitis is commonly practised by ophthalmologists, no one method has clearly been demonstrated to be more effective than another. We surveyed 570 Fellows of the Royal Australian College of Ophthalmologists to determine what their methods of prophylaxis were and whether these differed for patients who developed endophthalmitis. METHODS: The questionnaire asked about the types of antibiotics and other methods of prophylaxis used before, during and after cataract surgery. Of those who reported cases of endophthalmitis, we asked specifically about the methods of prophylaxis used for those patients. RESULTS: The response was 89% and the incidence of endophthalmitis was calculated as 0.11%. There was little difference in the methods of prophylaxis used by those who reported endophthalmitis compared with others, but pre-operative antibiotics were used more commonly by those who reported the disease (P = 0.06). Surgeons who had practised for 20 years or more reported a lower rate of endophthalmitis than others, as did those who performed more than 300 cataract operations per year. However the pattern of prophylaxis used by these two sub-groups was quite divergent. Differences in the methods of prophylaxis had no bearing on the development of endophthalmitis, with the exception that subconjunctival antibiotics were used less often in those patients who developed the disease (P = 0.03). CONCLUSIONS: The results of the present study provide no clear answer regarding appropriate peri-operative prophylaxis. The wide range of prophylactic regimens used suggests that no one method is superior to another. Formal case-controlled studies are required to identify which method would be most efficacious.

Antibiotic Prophylaxis↗
PubMed1998

Natural history of recurrent erosion syndrome--a 4 year review of 117 patients.

AIMS/BACKGROUND: Recurrent erosion syndrome encompasses a group of mixed aetiologies for which there are a number of methods of management which may influence the course of the disease. METHODS: The outcomes of a cohort of patients initially treated with topical lubricants were studied. 117 consecutive patients presenting over 1 year with a history of recurrent erosions were enrolled, baseline characteristics were documented, and treatment with lubricants was initiated. Patients were surveyed 4 years later inquiring about symptoms and treatments required. RESULTS: A total of 94 (80%) of the initial cohort were contacted. The mean age was 44 years and the sex distribution was 44 males to 50 females. The mean period of follow up was 48 months. 55 (59%) were still symptomatic with attacks occurring at a median frequency of 60 days. 13 patients (24%) complained of an episode at least every week and 28 patients (51%) suffered at least every month. The median pain score (analogue scale of 1-10) was 2.5. Seventy five per cent (n = 21) of patients with epithelial basement membrane dystrophy (EBMD) were symptomatic compared with those with a traumatic aetiology among whom 46% (n = 28) were symptomatic. This difference was significant (p = 0.02). Those with EBMD were more likely to be continuing to use topical lubricants than the trauma group. CONCLUSION: Patients with a traumatic aetiology are less likely to suffer chronic recurrent erosion syndrome than those with EBMD.

Administration, Topical↗
PubMed1998

Reliable keratometry with a new hand held surgical keratometer: calibration of the keratoscopic astigmatic ruler.

AIM: Some surgeons consider hand held surgical keratometers unreliable. This may be due to incorrect use through not realising that the distance that the keratometer is held from the cornea influences the shape of the image. When a keratometer is held closer to the astigmatic cornea, the elliptical image will appear more circular, particularly for larger degrees of astigmatism. However, the keratoscopic astigmatic ruler (KAR) has design features that correct the hitherto unrecognised problems with the use of a hand held keratometer. This study assesses the reliability and accuracy of measurement of astigmatism using the KAR. METHODS: The KAR and the Bausch & Lomb keratometer (B&L) were compared using six back surface toric cut contact lens blanks representing 1 to 6 dioptres of astigmatism. Two observers (one experienced in the use of the keratometers, the other a novice) took eight randomly repeated "masked" measurements of each lens blank with the KAR and four measurements with the B&L in a similar fashion. RESULTS: There was no difference between the measurements with either instrument by each of the observers (p = 0.95, ANOVA). The standard error of measurement for the KAR was 0.59 D, for the B&L, 0.31 D. The intraclass correlation coefficient of reliability for the KAR was 0.90 and for the B&L it was 0.97. The coefficient of repeatability for the KAR was plus or minus 0.83 D, and for the B&L plus or minus 0.77 D. The interobserver reliability for the KAR was 0.898, and for the B&L, 0.975. CONCLUSION: These results suggest that the KAR has good reliability and reproducibility and compares favourably with the B&L keratometer. Inexperience with use does not affect reliability.

Analysis of Variance↗
PubMed1998

Polymerase chain reaction analysis of corneal epithelial and tear samples in the diagnosis of Acanthamoeba keratitis.

PURPOSE: Acanthamoeba is an uncommon cause of corneal infection in which the best visual outcome follows prompt diagnosis and a long course of appropriate antimicrobial therapy. Because conventional detection techniques for Acanthamoeba have certain limitations, we investigated the ability of the polymerase chain reaction (PCR) to confirm the clinical diagnosis of Acanthamoeba keratitis, with the ultimate aim of achieving early diagnosis. METHODS: Using two different pairs of primers, PCR was performed on representative cultured Acanthamoeba isolates to confirm the assay's ability to amplify Acanthamoeba DNA from a wide range of acanthamoebae. Subsequently, corneal epithelial samples from 19 patients and tear samples from 12 patients with Acanthamoeba keratitis were analyzed by PCR for the presence of Acanthamoeba DNA. RESULTS: Acanthamoeba DNA was amplified by PCR from 16 (84%) of 19 corneal epithelial samples, whereas Acanthamoeba was cultured from 10 samples (53%), all of which were PCR positive. Tear samples from 8 (66%) of 12 patients were positive on PCR testing, and one tear sample was PCR positive, whereas the corresponding epithelial biopsy had yielded a negative PCR result. Samples from culture-positive patients were positive on PCR testing more frequently than those from culture-negative patients (10/10 culture-positive corneal epithelial and 5/7 [71%] culture-positive initial tear samples versus 6/9 [66%] culture-negative corneal epithelial and 2/5 [40%] culture-negative tear samples). All control epithelial (n = 15) and tear (n = 15) samples yielded negative results. CONCLUSIONS: PCR was a more sensitive diagnostic test than a culture for Acanthamoeba keratitis, and the use of two different primers achieved better sensitivity than a single set. A PCR of a tear sample also may be a useful complementary test and, in combination with PCR of epithelial samples, would prove particularly helpful in confirming the clinical diagnosis in culture-negative cases.

Acanthamoeba↗
PubMed1997

Outcome of acanthamoeba keratitis treated with polyhexamethyl biguanide and propamidine.

OBJECTIVE: This study investigates the clinical outcome of Acanthamoeba keratitis treated with polyhexamethyl biguanide (PHMB) and propamidine isethionate (Brolene). DESIGN: A retrospective review of all patients treated for Acanthamoeba keratitis between September 1992 and February 1995 was carried out. All patients were treated with PHMB 0.02% and propamidine 0.1% hourly for 3 days, the frequency reduced to four to six times daily according to clinical response. MAIN OUTCOME MEASURES: Age, gender, result of laboratory investigation, duration of disease before diagnosis, visual acuity (VA) pretreatment and post-treatment, need for keratoplasty, and presence of adverse reaction were measured. RESULTS: One hundred eleven cases were identified in 105 patients (60 male, 45 female; mean age, 32). Ninety-two percent of infections were in contact lens wearers. The clinical diagnosis was confirmed by corneal culture or histopathology in 64 cases (57.7%). The diagnosis was made "early" (within 28 days) in 65 cases (58.6%). Twenty-one (18.9%) were "intermediate" (28 days-2 months) and 20 (18%) were "late" (> 2 months) diagnoses. Overall post-treatment VA was 6/12 or better in the majority (88/111, 79.3%) of cases, and 18 (16.2%) had VA of 6/36 or worse. The VA of > or = 6/12 was achieved by 90.8% of the early, 71.4% of the intermediate, and 65% of the late groups. Clinical relapses occurred in 19 patients on reducing the therapy. Treatment toxicity was never serious and consisted only of stinging or superficial punctate keratopathy. Keratoplasty was indicated in only ten patients, and disease activity was controlled adequately in all patients before grafting. CONCLUSIONS: Combined treatment with PHMB and propamidine is well tolerated, nontoxic, and effective. Typically, visual outcome is favorable and the requirement for keratoplasty reduced markedly.

Acanthamoeba↗
PubMed1997

A method of drop administration.

Self-administering drops can be a daunting task for many patients. The authors describe a method of drop administration that allows a patient to accurately place drops without the need for special devices or touching the eye. With the bottle of drops held upside down, the back of the thumb is rested on the forehead to stabilize the bottle. The bottle tip can be seen over the eye. The other hand retracts the inferior lid to catch the drop. Poor compliance is common and is often caused by difficulties with drop administration. This simple technique may improve compliance.

Humans↗
PubMed1996

Topical interferon alpha 2b for corneal haze after excimer laser photorefractive keratectomy. The Melbourne Excimer Laser Group.

PURPOSE: To determine whether topical interferon alpha 2b (IFN-alpha) prevents corneal haze after excimer laser photorefractive keratectomy (PRK). SETTING: Tertiary referral ophthalmic hospital. METHOD: A prospective, double-blind, placebo-controlled, randomized study of 31 patients was undertaken. After surgery in a single institution, patients received a drop of either a placebo or IFN-alpha (5 x 10(6) IU/ml) four times daily for 4 weeks. The main outcome measures were corneal haze, refraction, and visual acuity. RESULTS: The major side effect of interferon alpha treatment was a significant delay in epithelial healing by a mean of 2 days. The means of the average post-treatment clinical scores for haze in all patients up to 12 months after surgery were 0.46 +/- 0.25 for the IFN-alpha group and 0.64 +/- 0.43 for the placebo group (P = .20). Of patients with a correction of greater than 5.00 diopters (D), the IFN-alpha group had significantly less haze over the course of the study (0.39 +/- 0.23 versus 0.98 +/- 0.50; P = .03). After 12 months, the mean absolute spherical equivalent in the two groups was not significantly different (1.02 +/- 1.13 D versus 1.44 +/- 2.64 D). There was a tendency toward better uncorrected visual acuity in the INF-alpha group (P < .10, Kolmogorov-Smirnov). CONCLUSION: Topical IFN-alpha may merit further investigation as a treatment to reduce corneal haze after excimer laser PRK for corrections greater than 5.00 D.

Administration, Topical↗