Iatrogenic macula hole and consequent macular detachment caused by intravitreal trypan blue injection.
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Aged↗
Biomedical subjects
R L Burton
Publications and source records attributed to R L Burton.
Acute postural drop in optic nerve perfusion after vitrectomy and gas in a patient with diabetic autonomic neuropathy.
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Acute Disease↗
B lymphoblastoid cell lines as efficient APC to elicit CD8+ T cell responses against a cytomegalovirus antigen.
Potent and readily accessible APC are critical for development of immunotherapy protocols to treat viral disease and cancer. We have shown that B lymphoblastoid cell lines (BLCL) that stably express CMV phosphoprotein 65 (BLCLpp65), as a result of retroviral transduction, can be used to generate ex vivo CTL cultures that possess cytotoxicity against CMV and EBV. In this report, we demonstrate that the EBV-specific cytotoxicity in the BLCLpp65-primed culture had a spectrum of EBV-Ag recognition similar to that of the BLCL-primed counterpart, suggesting that retroviral transduction and expression of the CMV Ag would not compromise the Ag-presenting capacity of BLCL. In addition, BLCLpp65 appeared to present multiple natural pp65 epitopes, because pp65-specific CTL, which recognized different CMV clinical isolates, were generated in BLCLpp65-primed cultures from individuals with various HLA backgrounds. Consistent with a polyclonal expansion of virus-specific CTL, T cell lines established from the BLCLpp65-primed CTL cultures expressed different TCR-Vbeta Although most of the virus-specific T cell isolates were CD8+, EBV-specific CD4+ lines were also established from BLCLpp65-primed cultures. Western blot analysis revealed that the CD8+ lines, but not the CD4+ line, expressed granzyme B, consistent with features of classic CTL. Thus, our results suggested that BLCL stably expressing a foreign Ag might be used as a practical APC to elicit CD8+ T cell responses.
Antigen-Presenting Cells↗
A phase I-II trial to examine the toxicity of CMV- and EBV-specific cytotoxic T lymphocytes when used for prophylaxis against EBV and CMV disease in recipients of CD34-selected/T cell-depleted stem cell transplants.
Epstein-Barr virus (EBV)-induced lymphoproliferative disease and cytomegalovirus (CMV) infection are major causes of morbidity and mortality in individuals with compromised cellular immunity. Although anti-viral pharmacological agents exist, severe side effects such as myelosuppression often limit the application of these medications. Infusion of ex vivo-expanded, virus-specific cytotoxic T-lymphocytes (CTL) has been proven to be safe and efficacious for the prophylaxis and treatment of EBV and CMV complications. While EBV-specific CTL can be readily and reliably produced with EBV-immortalized B-lymphoblastoid cell lines (BLCL) as stimulators, current protocols for CMV-specific CTL, which use CMV-infected fibroblasts as stimulators, may be associated with alloreactivity and the need for cloning, as well as the potential for exposure to human blood-born infectious agents. Our laboratory has developed a novel system to generate EBV/CMV-bi-specific CTL by co-culturing PBMC with autologous BLCL expressing a CMV protein pp65 (BLCLpp65) (Sun et al., 1999). pp65, an immunodominant CMV antigen, is transduced into BLCL by a recombinant retrovirus MSCVpp65. While low in alloreactivity, BLCLpp65-stimulated CTL are cytolytic to autologous cells infected with EBV or CMV, and this cytotoxicity is mediated by polyclonal, CD8+, MHC Class I-restricted T-cells. Further experiments revealed that retroviral transduction and expression of pp65 do not compromise the capacity of presenting EBV antigens, and T cells stimulated by BLCLpp65 recognize clinical strains of CMV (Sun et al., 2000). These data indicated that BLCLpp65 could substitute for BLCL as antigen presenting cells in adoptive immunotherapy against EBV-LPD, with the benefit of providing protection against CMV reactivation. This protocol is a Phase I/II study to examine the toxicity associated with and the immunologic effects of ex vivo simultaneously expanded EBV- and CMV-specific CTL for prophylaxis against EBV and CMV complications in recipients of CD34 selected/T-cell depleted stem cell transplants (SCT). EBV/CMV-specific CTL will be generated from peripheral blood mononuclear cells (PBMC) of EBV/CMV-seropositive donors in a course of from 21-28 days by weekly stimulation with autologous BLCLpp65. Qualified CTL will be administered to consenting patients at 40, 60, and 80 days post-transpOFF criteria of molecular virology and immunological reconstitution, which include blood levels of pp65 antigen and EBV viral DNA, and virus-specific CTL precursor frequency. Patients will also be tested for replication-competent retrovirus at 3, 6, and 12 month intervals post-transplant to ensure bio-safety.
Adolescent↗
Does preservative-free lignocaine 1% for hydrodissection reduce pain during phacoemulsification?
PURPOSE: To compare preservative-free 1% lignocaine with balanced salt solution (BSS) in alleviating pain during hydrodissection in phacoemulsification cataract surgery. SETTING: West Norwich Hospital, Norfolk, United Kingdom. METHODS: This prospective double-masked trial comprised 68 patients having day-case phacoemulsification cataract surgery. Patients were randomly divided into 2 groups, receiving either BSS or lignocaine 1% solution for hydrodissection during routine uneventful phacoemulsification using topical anesthesia. The level of intraoperative pain was scored on a scale of 0 (no pain) to 10 (severe pain), and the scores between the 2 groups were compared. RESULTS: Of the 68 patients, 33 (49%) received BSS and 35 (51%), lignocaine 1% solution. A pain score greater than 2 was considered clinically significant; 28 patients (85%) in the BSS group and 25 (71%) in the lignocaine 1% group scored 2 or less. The chi-square and Mann-Whitney tests found no significant difference between the BSS and lignocaine 1% groups (P = .30 and P = .432, respectively). CONCLUSION: There was no significant difference in the pain scores in patients who received BSS or lignocaine 1% solution. Thus, we conclude that hydrodissecting with lignocaine 1% solution does not provide added pain relief during phacoemulsification.
Anesthesia, Local↗
Phacoemulsification cataract surgery: is routine review necessary on the first post-operative day?
PURPOSE: To determine the value of routine review on the first post-operative day following phacoemulsification cataract surgery. METHODS: A prospective study was performed of 238 consecutive patients who underwent phacoemulsification cataract surgery. Local anaesthesia was used for 97% of patients and surgery was performed as a day-case procedure for 93% of patients. The findings at the first day post-operative review were analysed separately for patients who had undergone uncomplicated surgery and patients who had suffered an intraoperative complication. Four patients were excluded because of incomplete data collection. RESULTS: A total of 227 patients underwent uncomplicated phacoemulsification cataract surgery. Thirteen (5.7%, 95% confidence interval (CI) 3.1-9.6%) of these were found to have post-operative complications at their first day review which comprised corneal oedema (4.4%, 95% CI 2.1-8.0%), raised intraocular pressure > or = 30 mmHg (1.3%, 95% CI 0.3-3.8%), hyphaema (0.9%, 95% CI 0.1-3.1%), corneal abrasion (0.4%, 95% CI 0.0-2.4%) and anterior uveitis (0.4%, 95% CI 0.0-2.4%). These findings led to the standard post-operative management being altered for 5 (2.2%) patients. Intraoperative complications occurred in 7 (2.9%) patients during phacoemulsification cataract surgery. Five (71%) of these patients had post-operative complications at their first day review. CONCLUSIONS: Routine review on the first post-operative day following uncomplicated phacoemulsification cataract surgery could safely be withdrawn. A single post-operative review at 1-2 weeks after surgery would then be required, supplemented by patient-initiated post-operative review in the interim.
Aftercare↗
The phacoemulsification learning curve: per-operative complications in the first 3000 cases of an experienced surgeon.
PURPOSE: To assess the per-operative complications occurring during the first 3000 phacoemulsification cases performed by an experienced consultant surgeon. METHODS: A prospective analysis of 3000 consecutive cases performed without supervision between November 1992 and November 1998 was carried out. Data recorded for each case included details of per-operative complications, pre-operative best corrected visual acuity, nuclear density, history of previous pars plana vitrectomy, and whether phacoemulsification was performed as part of a phacotrabeculectomy procedure. RESULTS: The overall rate of vitreous loss was 1.3%. Nuclear fragments were lost to the vitreous in 6 cases (0.2%). The initial rate of vitreous loss was 4.0% in the first 300 cases falling to 0.7% in the last 300 cases. Capsulorhexis failure was the commonest per-operative complication observed, but the risk of subsequent posterior capsule rupture fell significantly from 9 of 45 (20.0%) in the first 100 cases to 1 of 49 (2.0%) in the next 2000 cases (p = 0.0061, Fisher's exact test). There was a significant increase in risk with denser cataracts, especially for capsulorhexis failure, rising to over 35% in the densest cases. The increases in posterior capsule rupture and vitreous loss were less dramatic but nonetheless very significant. There was no significant increase in the risk of per-operative complications with phacotrabeculectomy, and no increased risk in patients who had previously undergone pars plana vitrectomy. Posterior capsule rupture occurred in 22 of 612 (3.6%) local anaesthesia cases compared with 31 of 2269 (1.4%) topical anaesthesia cases. Per-operative best corrected visual acuity of 6/9 or better was recorded in 2.0% of the first 1000 cases compared with 13.9% of the last 1000 cases. CONCLUSIONS: (1) Per-operative surgical risks could be reduced to low levels during the learning curve, but complications continued to occur at a low frequency. (2) The risk of per-operative complications was not significantly elevated in previously vitrectomised eyes. (3) Nuclear density correlated significantly with per-operative complication risk. (4) The visual threshold for cataract surgery fell dramatically with increasing experience of phacoemulsification. (5) Topical anaesthesia was not associated with an increased risk of per-operative complications.
Anesthesia, Local↗
Simultaneous ex vivo expansion of cytomegalovirus and Epstein-Barr virus-specific cytotoxic T lymphocytes using B-lymphoblastoid cell lines expressing cytomegalovirus pp65.
Cytomegalovirus (CMV) infection and Epstein-Barr virus (EBV)-induced lymphoproliferative disease are serious complications associated with allogeneic stem cell transplantation. Immunotherapy using ex vivo expanded, virus-specific cytotoxic T lymphocytes (CTL) has been explored and proven to be effective in therapeutic or prophylactic regimens for CMV and EBV infections. To generate CTL specific for both CMV and EBV, we engineered EBV-transformed B-lymphoblastoid cell lines (BLCL) to express CMV pp65 for use as antigen-presenting cells (APC). BLCL were transduced with a recombinant retrovirus encoding pp65, the immunodominant CMV polypeptide. Western blot analysis and immunocytochemistry confirmed the expression of pp65 in the transduced cells. Peripheral blood mononuclear cells (PBMC) from healthy CMV seropositive donors were stimulated with autologous pp65-expressing BLCL weekly for 3 weeks. Chromium release assays showed that the resulting CTL cultures possessed specific cytotoxicity against EBV and CMV. Recombinant vaccinia viruses encoding individual CMV peptides were used to demonstrate that this CMV-specific cytotoxicity was specific for pp65. Assays on CD4- and CD8-depleted CTL fractions indicated that CD8(+) CTL mediated the pp65-specific cytotoxicity. These CMV/EBV-specific CTL recognized CMV- and EBV-infected targets sharing HLA class I antigens, but not HLA mismatched targets. Our results demonstrate that BLCL can be used as APC to stimulate expansion of EBV- and CMV-specific CTL simultaneously. These findings have potential implications for posttransplant CMV and EBV immunotherapy in recipients of allogeneic stem cell transplants.
Antigens, Viral↗
CD4(+) Epstein-Barr virus-specific cytotoxic T-lymphocytes from human umbilical cord blood.
Umbilical cord blood (CB) is increasingly used for allogeneic hematopoietic stem cell transplantation. To determine whether viral antigen-specific cytotoxic T-lymphocytes (CTL) could be generated from the predominantly naive T-cell populations in CB, CB-derived mononuclear cells were stimulated with autologous Epstein-Barr virus (EBV) transformed B-lymphoblastoid cell lines over several weeks in the presence of recombinant human interleukin-2 (IL-2). By 28 days of culture, T-lymphocytes from all six CB that had been treated with IL-2 displayed EBV-specific cytotoxicity. These cells were largely CD4(+), with complete inhibition of cytotoxicity by anti-CD3 and variable inhibition by anti-HLA DR monoclonal antibodies. The EBV-specific effectors were cloned by limiting dilution, and most of the CTL clones were CD4(+). The cytotoxicity of the CB-derived CD4(+) CTL clones was inhibited by EGTA but not by anti-Fas ligand mAb, suggesting that this cytotoxicity was mediated by perforin/granzyme B. These data indicate that virus-specific CTL can be cultivated and cloned from CB, a human T-cell source that may not have prior in vivo antigenic exposure or reactivity. This finding may have applications in adoptive immunotherapy to recipients of CB transplants.
Adult↗
Primary vitrectomy for pseudophakic and aphakic retinal detachments.
PURPOSE: To evaluate primary vitrectomy for the treatment of pseudophakic and aphakic retinal detachments. Primary vitrectomy may enable better identification of retinal breaks than scleral buckling procedures. METHODS: A prospective study was performed of primary vitrectomy for the treatment of 25 consecutive cases of pseudophakic and aphakic retinal detachment. RESULTS: The primary retinal reattachment rate was 84% (21 eyes). Surgical failure resulted from new/missed retinal breaks (2 eyes) and proliferative vitreoretinopathy (2 eyes). The final retinal reattachment rate with further surgery was 96% (24 eyes). There were 7 macula-on detachments which all retained their presenting visual acuity. A visual acuity of 6/18 or better was achieved by 56% of the 18 macula-off detachments. Visualisation of the peripheral retina was impaired in 17 eyes and procedures to improve visualisation were performed in 7 eyes. Retinal breaks were detected in 16 eyes at surgery that had not been identified pre-operatively. Raised intraocular pressure was the most common complication, affecting 10 eyes in the early post-operative period. CONCLUSIONS: Primary vitrectomy offers certain advantages in the treatment of pseudophakic and aphakic retinal detachments. A controlled study is required to determine whether primary vitrectomy achieves a better outcome than scleral buckling procedures for these retinal detachments.
Adult↗
Endogenous endophthalmitis due to group G streptococcus.
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Aged↗
Semiquantitative Epstein-Barr virus (EBV) polymerase chain reaction for the determination of patients at risk for EBV-induced lymphoproliferative disease after stem cell transplantation.
Epstein-Barr virus-induced lymphoproliferative disease (EBV-LPD) is a serious and potentially fatal complication after allogeneic stem cell transplantation (SCT). To evaluate levels of EBV DNA in SCT patients, a semiquantitative polymerase chain reaction (PCR) assay was developed. DNA was extracted from peripheral blood leukocytes and diluted, and PCR was performed by using a primer set specific for a well-conserved sequence of the internal repeat 1 region of the EBV genome. Forty-one SCT patients were screened with this method. Thirty-seven patients received allogeneic transplants, of which 18 were T-cell-depleted marrow. Four additional patients received autologous SCT, one of which was T-cell depleted. The mean time of follow-up by EBV PCR was 147 days (range, 47 to 328 days) posttransplant. The range of EBV copies/microg DNA from normal EBV sero-positive donors was 40 to 4,000. Seven patients had >/=40,000 copies of EBV DNA/microg DNA, all of whom were recipients of T-cell-depleted SCT. Five of the seven patients with elevated levels of EBV DNA developed EBV-LPD. Four of these five patients with EBV-LPD had elevated levels of EBV DNA from 1 to 8 weeks before diagnosis. Two patients with EBV-LPD had normal levels of EBV DNA, and two patients with >/=40,000 copies EBV/microg DNA did not develop EBV-LPD. In one patient, clinical resolution of disease correlated with a decrease in EBV DNA and an increase in the level of EBV-specific cytotoxic T-cell precursors. These data indicate that the measurement of EBV viral load with semiquantitative PCR is useful in detecting EBV-LPD in high-risk patients before the onset of clinical symptoms. Because not all patients with elevated levels of EBV DNA develop EBV-LPD, semiquantitative PCR results cannot substitute for clinical, radiographic, and pathological confirmation of this diagnosis.
Adolescent↗
Contrast sensitivity after implantation of diffractive bifocal and monofocal intraocular lenses.
PURPOSE: To compare contrast sensitivity (CS) after implantation of a diffractive bifocal intraocular lens (IOL) and a monofocal IOL of similar design. SETTING: Seven European centers. METHODS: In this randomized, prospective study, CS was tested 5 months after cataract and IOL implantation surgery in 115 patients with a diffractive bifocal IOL and 106 patients with a monofocal IOL. It was also tested in a subgroup of 38 patients who had bilateral implantation of a diffractive bifocal IOL. Contrast sensitivity was tested using the Vision Contrast Test System (VCTS). RESULTS: In patients with a best corrected visual acuity (BCVA) of 1.0 or better, the CS at all spatial frequencies (1.5 to 18 cycles/degree), both at distance and near, was slightly lower in the bifocal IOL group than in the monofocal group. Mean values were within the normal range. In patients with a BCVA of less than 1.0, the CS was lower and the difference between the bifocal and monofocal groups was less. In patients with bilateral bifocal IOLs, CS was better when tested bilaterally than when testing the better eye alone. Pupil size affected the results to a small degree. Contrast sensitivity appeared to improve over time after implantation of a diffractive bifocal IOL. CONCLUSIONS: In patients with cataract and no other eye pathology, the diffractive bifocal IOL with slightly reduce the CS at all spatial frequencies. In those with reduced visual acuity after cataract surgery, CS will be reduced accordingly. In this situation, the reduction from the diffractive bifocal optic would be minor.
Aged↗
Comparison of a diffractive bifocal and a monofocal intraocular lens.
PURPOSE: To compare a Pharmacia diffractive bifocal intraocular lens (IOL) with a monofocal lens of the same design without the diffractive grating. SETTING: Multicenter study. METHODS: This randomized, prospective study comprised 70 patients with a monofocal IOL and 79 with a diffractive bifocal IOL. Follow-up was 5 to 6 months. Near and distance visual acuities, contract sensitivity, patient satisfaction, and spectacle use were evaluated. RESULTS: All patients achieved a best corrected visual acuity of 0.5 or better; 80% in the monofocal and 71% in the bifocal group had a best corrected visual acuity of 1.0 or better. Without correction, 93% of the bifocal and 9% of the monofocal group could read J3 or better. With distance correction, 99% and 4%, respectively, could read J3 or better. Contrast sensitivity was slightly lower in the bifocal group at distance and near for all spatial frequencies. In the bifocal group, 46% never used spectacles for near tasks. Overall satisfaction was rated good by 86% of the monofocal and 85% of the bifocal group. CONCLUSIONS: The diffractive bifocal IOL performed well at distance and near. Patients who no longer require spectacles will benefit significantly from a bifocal IOL, but many with a bifocal IOL in one eye will require spectacles for the fellow eye.
Aged↗
Randomised trial of topical versus sub-Tenon's local anaesthesia for small-incision cataract surgery.
Fifty unselected patients undergoing routine cataract surgery were randomised to receive either topical or sub-Tenon's local anaesthesia with 2% prilocaine administered by a blunt cannula. Visual analogue scales were used to assess pain during administration of sub-Tenon's anaesthetic and pain during surgery, and any complications were noted. Sub-Tenon's anaesthesia proved to be entirely comfortable to administer, and allowed for a statistically significantly more pain-free operation, at the expense of some residual eye movement and an inevitable subconjunctival haemorrhage. Both techniques compared well with other studies assessing periorbital or retro-orbital injections, and both have significant safety advantages which are discussed in the context of the joint Royal Colleges report on ophthalmic anaesthesia. It is suggested that a combination of one or other technique could safely cover all requirements for intraocular surgery under local anaesthesia.
Administration, Topical↗
Extracapsular cataract surgery using capsulorhexis with viscoexpression via a limbal section.
Two hundred consecutive patients had extracapsular cataract surgery by capsulorhexis and viscoexpression. Capsulorhexis, attempted in 195 eyes, was successful in 87.7%. Viscoexpression was attempted in 162 cases and successfully delivered the nucleus in 87.7%. There were five cases of zonule rupture, one of posterior capsule rupture, and two of vitreous loss. If the capsulorhexis is larger than 5 mm, viscoexpression can be safely used on all cataracts, regardless of nuclear density, and is the ideal transition to phacoemulsification.
Cataract Extraction↗
Genetic variation and phylogenetic relationships among worldwide collections of the Russian wheat aphid, Diuraphis noxia (Mordvilko), inferred from allozyme and RAPD-PCR markers.
Genetic analyses were conducted on Diuraphis noxia (Mordvilko) populations collected from wheat, barley and other grasses from various countries throughout the world. These collections had been found to contain clones that differed in virulence from various cultivars, cuticular hydrocarbon profiles and life cycle characters. Discrete genetic markers analysed in this study included allozymes and arbitrary regions of the genome amplified by the polymerase chain reaction (RAPD-PCR). In all, 23 enzymes were evaluated; 17 of these enzymes representing 20 isozyme loci, were judged suitable for allozyme analysis. Polymorphisms were detected at three (15 per cent) loci: beta-esterase (beta-EST), phosphoglucose isomerase (PGI), and 6-phosphogluconate dehydrogenase (6-PGDH). The average expected heterozygosity amongst these loci was 4.9 per cent in the worldwide collection. Allozyme variation was absent within most populations, particularly within those countries where the species was recently introduced. Much greater genetic variation was detected when populations were analysed with RAPD-PCR. Populations were analysed with 69 polymorphic bands amplified by seven primers. All populations could be distinguished with this method. Cluster analyses indicated strong similarities between U.S.A. populations and collections from South Africa, Mexico, France and Turkey. The most variation was detected among populations from the Middle East and southern Russia.
Animals↗
Needle drainage of subretinal fluid. A randomized clinical trial.
Needle drainage of subretinal fluid with simultaneous observation using the indirect ophthalmoscope has been reported to have a very low complication rate. The technique was evaluated by a prospective clinical trial. The study group consisted of 100 patients undergoing scleral buckling for rhegmatogenous retinal detachment who were randomly assigned to groups treated with needle drainage or conventional two-stage drainage. At 1 month, the retina was anatomically flat in 88% of all cases. Subretinal hemorrhage occurred in 10 of 45 patients (22.2%) after needle drainage and in 7 of 55 patients (12.7%) after conventional drainage. The difference was not statistically significant. Retinal puncture occurred during conventional drainage in one case and in no cases during needle drainage. There were no cases of retinal incarceration. The results showed that subretinal hemorrhage was more common after needle drainage, but a larger study would be required to show whether this difference was statistically significant. The fear that the retina would be damaged by placement of a needle in the subretinal space throughout the drainage procedure was unfounded.
Aged↗