Anti-infective photodynamic biomaterials for the prevention of intraocular lens-associated infectious endophthalmitis

Bacterial attachment onto intraocular lenses (IOLs) during cataract extraction and IOL implantation is a prominent aetiological factor in the pathogenesis of infectious endophthalmitis. Photodynamic therapy (PDT) and photodynamic antimicrobial chemotherapy (PACT) have shown that photosensitizers are effective treatments for cancer, and in the photoinactivation of bacteria, viruses, fungi and parasites, in the presence of light. To date, no method of localizing the photocytotoxic effect of a photosensitizer at a biomaterial surface has been demonstrated. Here we show a method for concentrating this effect at a material surface to prevent bacterial colonization by attaching a porphyrin photosensitizer at, or near to, that surface, and demonstrate the principle using IOL biomaterials. Anionic hydrogel copolymers were shown to permanently bind a cationic porphyrin through electrostatic interactions as a thin surface layer. The mechanical and thermal properties of the materials showed that the porphyrin acts as a surface cross-linking agent, and renders surfaces more hydrophilic. Importantly, Staphylococcus epidermidis adherence was reduced by up to 99.0 ± 0.42% relative to the control in intense light conditions and 91.7± 5.99% in the dark. The ability to concentrate the photocytotoxic effect at a surface, together with a significant dark effect, provides a platform for a range of light-activated anti-infective biomaterial technologies.

Fundus autofluorescence in the diagnosis of cystoid macular oedema

Aim: To determine the sensitivity and specificity of the non-invasive imaging technique, fundus autofluorescence (AF), in the diagnosis of cystoid macular oedema (CMO), using fluorescein angiography as the reference standard. Design: Retrospective, consecutive, observational case series. Methods: Ninety-six consecutive patients with CMO suspected clinically were selected from the AF database of the Retina Unit, Ophthalmology Department, Grampian University Hospitals-NHS Trust, between August 2004 and June 2006. Only patients in whom CMO was secondary to (1) cataract extraction, (2) inherited retinopathies, (3) inflammatory eye disease or (4) idiopathic cases were included in this study. Only patients in whom AF images had been performed within 2 weeks of FFA and, when obtained following FFA, there was a minimum gap of 4 days ("washing out" period), were considered eligible for this study. A total of 34 eyes from 34 patients were eligible and were included in this study. FFA was used as the reference test to confirm the presence of CMO, and, based on fluorescein angiography (FFA), CMO was graded as either mild or florid. AF images were examined in a masked fashion for the presence or absence of CMO. The sensitivity and specificity of AF in detecting CMO were then calculated. Results: CMO was seen on AF imaging as round or oval areas at the fovea with an AF signal similar to that of background levels. At this site (fovea), the AF signal is usually reduced compared with background, due to the blockage caused by luteal pigment. The diagnosis of CMO based on AF imaging had 81% sensitivity and 69% specificity when compared with the reference standard FFA. Based on the FFA, there were 12 cases of florid CMO and eight of mild CMO. Of the former, CMO was detected with AF imaging in 100% (12/12 eyes), and of the latter, in 50% (4/8 eyes). Conclusions: AF imaging can be used as a rapid, non-invasive technique in the diagnosis of CMO.

Pseudophakic retinal detachment

Pseudophakic retinal detachment is a rare, but potentially serious, complication of cataract surgery. The incidence of pseudophakic retinal detachment following current surgical techniques of cataract extraction, including extracapsular cataract extraction by nuclear expression and phacoemulsification, is lower than that found after intracapsular cataract extraction. The risk of pseudophakic retinal detachment appears to be increased in myopic patients, in those patients in whom vitreous loss had occurred at the time of cataract surgery, and in patients undergoing Nd:YAG posterior capsulotomy. Most cases present to the clinician when the macula is already detached and the central vision is affected. When evaluating patients with pseudophakic retinal detachment, the fundal view is often impaired by anterior or posterior capsular opacification, reflections related to the intraocular lens, or poor mydriasis. Scleral buckling, pneumatic retinopexy, and primary pars plana vitrectomy, with or without combined scleral buckling, are the surgical techniques used to treat pseudophakic retinal detachment. Anatomical success rates are high after vitreo-retinal surgery for pseudophakic retinal detachment, although a smaller proportion of patients recover good vision following surgery. © 2003 Elsevier Inc. All rights reserved.

Indications for penetrating keratoplasty and associated procedures, 1989-1995

Purpose. To identify changing trends in indications for penetrating keratoplasty and associated surgical procedures. Methods. Review of charts from all patients who underwent penetrating keratoplasty at Wills Eye Hospital from January 1, 1989 through December 31, 1995. Results. A total of 2,442 corneal transplants were performed in 2,186 patients. The leading indication for penetrating keratoplasty was pseudophakic corneal edema, accounting for 634 cases (26.0%); 54.7% of them were associated with anterior chamber intraocular lenses, 36.4% with posterior chamber intraocular lenses, and 3.1% with iris-fixated intraocular lenses. Regraft (17.8%), Fuchs' dystrophy (15.7%), and keratoconus (13.2%) followed pseudophakic corneal edema in frequency. Cataract extraction, with or without intraocular lens implantation, was combined with penetrating keratoplasty in 439 cases of 1,264 phakic eyes (34.7%). Intraocular lens exchange was performed in 285 of the 634 cases of pseudophakic cornea edema (44.9%). Conclusion. Pseudophakic corneal edema was the leading indication for penetrating keratoplasty, with an increasing number of cases associated with posterior chamber intraocular lenses during the study period (p = 0.001). The number of regrafts steadily increased between 1989 and 1995 (p = 0.001), being the second most common indication for corneal transplantation since 1992.

Surgical technique:Complex glaucoma case requiring molteno drainage tube extension

A 42-year-old man has been under long-term follow-up since he was a child for congenital glaucoma and buphthalmos in both eyes. His left eye best corrected visual acuity (BCVA) was counting fingers, due to end-stage glaucoma. He was on maximal medical therapy with an intraocular pressure (IOP) maintained at mid to low twenties. His right eye, the only seeing eye, had a BCVA of 6/9. This eye had undergone multiple glaucoma laser and surgical procedures, including an initial first Molteno drainage device inserted superonasally that failed in April 2003 due to fibrotic membrane over the tube opening. As a result, he subsequently had a second Molteno drainage device inserted inferotemporally. To further maximize his vision he had an uncomplicated cataract extraction and intraocular lens implant in December 2004, after which he developed postoperative cystoid macular edema and corneal endothelial failure. He underwent a penetrating keratoplasty in the right eye thereafter in March 2007. After approximately a year, the second Molteno device developed drainage tube retraction, which was managed surgically to maintain optimum IOP in the right eye. His right eye vision to date is maintained at 6/12. © 2011 Mustafa and Azuara-Blanco.

Malignant glaucoma after diode laser cyclophotocoagulation

PURPOSE: To report a case of malignant glaucoma after diode laser cyclophotocoagulation. METHOD: Case report. RESULTS: A 45-year-old man with uncontrolled secondary glaucoma in his right eye after corneoscleral graft and cataract extraction underwent diode laser cyclophotocoagulation. The right eye was aphakic, with an intact posterior capsule. Two weeks later, the patient presented with blurred vision, edematous cornea, and flat anterior chamber. The posterior capsule was touching the endothelium. Intraocular pressure was 20 mm Hg. Repeated Nd:YAG laser capsulotomy was effective in reversing the malignant glaucoma attack, and the anterior chamber deepened. CONCLUSION: Malignant glaucoma can occur after diode laser cyclophotocoagulation.

Amniotic membrane transplantation for ocular surface reconstruction

Aims - To evaluate the efficacy of amniotic membrane transplantation (AMT) for ocular surface reconstruction. Methods - 10 consecutive patients who underwent AMT were included. The indications were: group A, cases with persistent epithelial defect after corneal abscess (n = 1), radiation (n = 1), or chemical burn (n = 3); group B, cases with epithelial defect and severe stromal thinning and impending or recent perforation, due to chemical burn (two patients, three eyes) or corneal abscess (n = 2); group C, to promote corneal epithelium healing and prevent scarring after symblepharon surgery with extensive corneo-conjunctival adhesion (n = 1). Under sterile conditions amniotic membrane was prepared from a fresh placenta of a seronegative pregnant woman and stored at -70°C. This technique involved the use of amniotic membrane to cover the entire cornea and perilimbal area in groups A and B, and the epithelial defect only in group C. Results - The cornea healed satisfactorily in four of five patients in group A, but the epithelial defect recurred in one of these patients. After AMT three patients underwent limbal transplantation and one penetrating keratoplasty and cataract extraction. In group B amniotic membrane transplantation was not helpful, and all cases underwent an urgent tectonic corneal graft. Surgery successfully released the symblepharon, promoted epithelialisation and prevented adhesions in the case of group C. Conclusion - AMT was effective to promote corneal healing in patients with persistent epithelial defect, and appeared to be helpful after surgery to release corneo-conjunctival adhesion. Most surgery for further surface rehabilitation. Amniotic membrane used as a patch was not effective to prevent tectonic corneal graft in cases with severe stromal thinning and impending or recent perforation.

Pseudocapsulorrhexis in a patient with iridocorneal endothelial syndrome

We describe a patient with Chandler's syndrome variant of the iridocorneal endothelial syndrome in whom ectopic Descemet's membrane was found intraoperatively on the anterior surface of the lens. Initially, the membrane was confused with the anterior lens capsule during extracapsular cataract extraction, leading to the performance of a pseudocapsulorrhexis. Electron microscopy disclosed that the epilenticular membrane was composed of multiple layers of abnormal basement membrane consistent with the iridocorneal endothelial syndrome.

Role of glycation in modification of lens crystallins in diabetic and nondiabetic senile cataracts

To assess the significance of glycation, nonenzymatic browning, and oxidation of lens crystallins in cataract formation in elderly diabetic patients, we measured three distinct products of glycation, browning, and oxidation reactions in cataractous lens crystallins from 29 diabetic patients (mean +/- SD age 72.8 +/- 8.8 yr) and 24 nondiabetic patients (age 73.5 +/- 8.3 yr). Compounds measured included 1) fructoselysine (FL), the first stable product of glycation; 2) pentosidine, a fluorescent, carbohydrate-derived protein cross-link between lysine and arginine residues formed during nonenzymatic browning; and 3) N epsilon-(carboxymethyl)lysine (CML), a product of autoxidation of sugar adducts to protein. In diabetic compared with nondiabetic patients, there were significant increases (P less than 0.001) in HbA1 (10.2 +/- 3.1 vs. 7.1 +/- 0.7%), FL (7.6 +/- 5.4 vs. 1.7 +/- 1.2 mmol/mol lysine), and pentosidine (6.3 +/- 2.8 vs. 3.8 +/- 1.9 mumol/mol lysine). The disproportionate elevation of FL compared with HbA1 suggests a breakdown in the lens barrier to glucose in diabetes, whereas the increase in pentosidine is indicative of accelerated nonenzymatic browning of diabetic lens crystallins. CML levels were similar in the two groups (7.1 +/- 2.4 vs. 6.8 +/- 3.0 mmol/mol lysine), providing no evidence for increased oxidative stress in the diabetic cataract. Thus, although the modification of lens crystallins by autoxidation reactions was not increased in diabetes, the increase in glycation and nonenzymatic browning suggests that these processes may acclerate the development of cataracts in diabetic patients.

Angle-closure glaucoma: impact, etiology, diagnosis, and treatment.

PURPOSE OF REVIEW:

Recent studies underscore the importance of angle-closure glaucoma (ACG) as a cause of world blindness. A major contribution in assessing the true impact of this disease has been an article estimating the number of persons with occludable angles, angle closure, and blindness from ACG in China as 28.2 million, 9.1 million, and 1.7 million, respectively. Although these numbers are based on data from Singapore and Mongolia, which may be applied to China only with caution, they emphasize the blinding potential of ACG, which is three times as likely to be associated with blindness as open-angle glaucoma (OAG).

RECENT FINDINGS:

Recent reports in the Chinese literature on ACG prevalence suffer from definitional problems that would appear to lead to systematic overestimates of ACG prevalence and underestimates of OAG prevalence. Nonetheless, data from studies by Chinese investigators further emphasize the strong association between ACG and blindness, with fully 16% of subjects with ACG blind in one report-a far higher proportion than for OAG in China and elsewhere. The importance of topiramate as a cause of secondary angle closure has recently been understood, in part, because of a series of 19 such cases reported by investigators at the Food and Drug Administration.

SUMMARY:

Angle closure in this setting appears to be caused by uveal effusion and anterior rotation of the ciliary body with resultant closure of the angle. The condition is not always responsive to laser iridectomy, and elimination of the causative agent appears to be critical. Ultrasonic biomicroscopy is a potential new diagnostic modality for ACG, allowing the measurement of novel parameters, such as the angle opening distance (AOD) at 500 microm (AOD 500). The efficacy of such parameters in improving screening for ACG can only be established by prospective studies of potentially at-risk eyes. A number of novel treatments for AC and angle closure have recently been proposed, including cataract extraction, paracentesis, and argon laser iridoplasty. As with proposed new diagnostic modalities, the efficacy of these treatments remains to be demonstrated with prospective studies, ideally organized in a controlled, randomized fashion.

Cataract surgery induces retinal pro-inflammatory gene expression and protein secretion

To investigate the effect(s) of cataract surgery on the expression of pro-inflammatory genes and proteins in the retina using an experimental rodent model. An extracapsular lens extraction was performed in one eye of C57BL/6 mice (n=24); the contralateral unoperated eyes (n =24) as well as eyes from unoperated animals (n = 9) served as controls. The neurosensory retina and retinal pigment epithelium (RPE)/choroid were collected postoperatively. Expression of genes involved in the acute inflammatory/ injury response, including IL-1ß, fibroblast growth factor, transforming growth factor ß, chemokine CCL2, SDF-1, and complements C3, C4, and factor B (CFB), were examined by real-time PCR and, selectively, by immunohistochemistry. The expression of IL-1 ß and CCL2 genes was markedly upregulated (>0-fold, P >0.01) in the neurosensory retina 30 minutes postoperatively and maintained for the 2-week postoperative period of observation; IL-1 ß expression was also upregulated in RPE/choroid. The expression of complement C3 (>-fold) and CFB (>0-fold) genes in the neurosensory retina was also significantly upregulated (P

Extraction and radioimmunoassay quantitation of neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) from human dental pulp tissue

The measurement of neuropeptides in complex biological tissue samples requires efficient and appropriate extraction methods so that immunoreactivity is retained for subsequent radioimmunoassay detection. Since neuropeptides differ in their molecular mass, charge and hydrophobicity, no single method will suffice for the optimal extraction of various neuropeptides. In this study, dental pulp tissue was obtained from 30 human non-carious teeth. Of the three different neuropeptide extraction methods employed, boiling in acetic acid in the presence of protease inhibitors yielded the highest levels of neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP). High pressure liquid chromatography (HPLC) analysis of dental pulp tissue verified the authenticity of the neuropeptides extracted. © 2003 Elsevier Science Ltd. All rights reserved.

Determination of metformin in plasma using a new ion pair solid phase extraction technique and ion pair liquid chromatography

This article describes the development of the first ion pair solid phase extraction technique (IPSPE), which has been applied to the extraction of metformin from plasma samples. In addition an ion pair chromatographic method was developed for the specific HPLC determination of metformin. Several extraction and HPLC methods have been described previously for metformin, however, most of them did not solve the problems associated with the high polarity of this drug. Drug recovery in the developed method was found to be more than 98%. The limit of detection and limit of quantification was 3 and 5 ng/ml, respectively. The intraday and interday precision (measured by coefficient of variation, CV%) was always less than 9%. The accuracy (measured by relative error, R.E.%) was always less than 6.9%. Stability analysis showed that metformin is stable for at least 3 months when stored at -70degreesC. The method has been applied to 150 patient samples as part of a medication adherence study. (C) 2003 Elsevier B.V. All rights reserved.