Causes and outcomes for patients presenting with diplopia to an eye casualty department.

PURPOSE: To evaluate the causes and outcomes for patients presenting with diplopia to an eye casualty department. METHODS: Patients presenting with diplopia as a principal symptom, who were referred to the Orthoptic Department from Moorfields Eye Casualty over a 12-month period, were retrospectively investigated. RESULTS: One hundred and seventy-one patients were identified with complete records in 165 cases. There were 99 men and 66 women with an age range of 5-88 years. Monocular diplopia accounted for 19 cases (11.5%), whereas 146 patients (88.5%) had binocular diplopia. Cranial nerve palsies were the most common cause of binocular diplopia accounting for 98 (67%) of cases. Isolated sixth nerve palsy was the largest diagnostic group (n=45). Microvascular disease (hypertension or diabetes mellitus, or both) was present in 59% of patients with cranial nerve palsies, and of this group, 87% resolved spontaneously by 5 months rising to 95% by 12 months. CONCLUSION: Patients with clinically isolated single cranial nerve palsies associated with diabetes or hypertension are likely to recover spontaneously within 5 months and initially require observation only. However, patients with unexplained binocular diplopia and those who progress or fail to recover should be investigated to establish the underlying aetiology and managed as appropriate.

Baclofen for patients with congenital periodic alternating nystagmus.

PURPOSE: To describe the clinical effect of baclofen on a group of patients with congenital periodic alternating nystagmus. METHODS: A retrospective review of case notes was carried out of all patients with congenital periodic alternating nystagmus (PAN) treated with baclofen between 1999 and 2004. Eight patients were identified, 6 males and 2 females with a mean age of 21 years (range 9 to 34 years). Clinical data were recorded for all patients pre- and post-treatment with the GABA agonist baclofen. Adverse effects of the treatment were recorded and a questionnaire was constructed to evaluate patient satisfaction with the treatment. RESULTS: All 8 patients had an abnormal head posture (AHP) before treatment which improved following treatment in 4 patients, one of whom had recurrence following treatment withdrawal. Binocular Snellen visual acuity (VA) improved by one line in 4 cases, while none of the other 4 patients suffered any loss of vision from the treatment. Three of the eight patients have continued on treatment long-term, in one case for 6 years. In the other five, treatment was withdrawn due to side effects in 4 cases, and in the fifth due to a lack of effect. The most commonly reported side effect was drowsiness, which occurred in 3 patients. Using a patient-centered survey, complete responses were obtained from 6 of the 8 patients treated. Five patients were either pleased or very pleased that they had tried the treatment. The reasons given were: improved vision or head posture, an appreciation of slowing of ocular movements, improved cosmesis and improved confidence. CONCLUSIONS: Baclofen may be effective in a select group of patients with congenital PAN and a trial of treatment may be worthwhile, prior to considering surgical intervention in this condition.

Modulation of hydrogen peroxide induced injury to corneal endothelium by virus mediated catalase gene transfer.

AIM: To examine the effect of catalase gene transfer on survival of corneal endothelial cells (EC) following challenge with hydrogen peroxide (H(2)O(2)) in an ex vivo model of oxidative stress. METHODS: A recombinant adenovirus vector (AdCL) was used to transfer human catalase cDNA into EC of whole thickness rabbit corneas ex vivo. The resulting catalase protein concentration was measured in corneal lysates by ELISA; catalase functional activity in lysates was determined using a H(2)O(2) activity assay. To examine the morphological effects of catalase gene transfer in modulation of H(2)O(2) induced injury, transduced corneas were maintained in ex vivo culture and challenged with H(2)O(2). Laser scanning confocal microscopy was used to image EC injury. Cell density, cell morphology, and ratios of viable to necrotic cells were determined. RESULTS: Following incubation with AdCL, catalase expression reached maximum at 5-7 days. Corneas transduced with AdCL showed increased EC cell survival following challenge with H(2)O(2) on day 3 when compared to null vector control or mock infected corneas. CONCLUSIONS: Ex vivo catalase gene transfer can protect EC from death mediated by H(2)O(2). This gene based approach to the protection of corneal endothelium from oxidative stress may have application in prevention of EC loss in pathological conditions in which H(2)O(2) is involved and in ex vivo donor corneal storage before transplantation.

Penetrating keratoplasty in infants.

PURPOSE: To analyze graft survival and visual outcome after penetrating keratoplasty in infants with congenital corneal opacity. METHODS: We retrospectively reviewed the records of 11 patients with congenital corneal opacity who underwent penetrating keratoplasty as infants. Six patients had a diagnosis of Peter's anomaly, 1 of congenital hereditary endothelial dystrophy, 1 of posterior polymorphous dystrophy, and 2 of sclerocornea, and in the other patient, the cause of the opacity was unknown. RESULTS: In total, 26 penetrating keratoplasties were performed on 16 eyes of 11 infants. All patients initially underwent surgery before the age of 13 months. Five patients underwent bilateral penetrating keratoplasty, and 10 of the transplants were repeat operations on eyes that had already had at least one previously failed graft. The age of the infants at the time of first penetrating keratoplasty ranged from 2 to 56 weeks (median, 13 weeks). The graft survival time for all transplants ranged from 3 to 137 months (median, 16 months). Overall first graft survival at 12 months was 61% (95% CI, 33%-81%), with 10 of 16 eyes retaining a clear corneal graft. Peter's anomaly, lensectomy, and repeat penetrating keratoplasty were factors most highly associated with poor graft survival and a low final visual acuity. CONCLUSION: Early penetrating keratoplasty for congenital corneal opacity may prevent deprivation amblyopia. Although this procedure carries a high risk of failure, particularly in those patients with Peter's anomaly, careful case selection, optical correction, and management of postoperative amblyopia may result in a successful visual outcome.

Cytokine and chemokine expression kinetics after corneal transplantation.

BACKGROUND: Allogeneic rejection is the most common cause of corneal graft failure. The aim of this work was to establish the kinetics of cytokine and chemokine mRNA expression before and after onset of corneal graft rejection. METHODS: Intracorneal cytokine and chemokine mRNA levels were investigated in the Brown Norway-->Lewis inbred rat model in which rejection onset is observed at 8/9 days after grafting in all animals. Nongrafted corneas and syngeneic (Lewis-->Lewis) corneal transplants were used as controls. Donor and recipient cornea was examined by quantitative competitive reverse transcription-polymerase chain reaction (RT-PCR) for hypoxyanthine phosphoribosyltransferase (HPRT), CD3, CD25, interleukin (IL)-1beta, IL-1RA, IL2, IL-6, IL-10, interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), transforming growth factor (TGF)-beta1, and macrophage inflammatory protein (MIP)-II and by nonquantitative RT-PCR for IL4, IL-5, IL-12 p40, IL-13, TGF-beta2, monocyte chemotactic protein-1 (MCP-1), MIP-1alpha, MIP-1beta, and RANTES (for regulated upon activation normal T cell expressed and secreted). RESULTS: A biphasic expression of cytokine and chemokine mRNA was found after transplantation. During the early phase (days 3-9), there was an elevation of the majority of the cytokines examined, including IL-1beta, IL-6, IL-10, IL-12 p40, and MIP-II. There was no difference in cytokine expression patterns between allogeneic or syngeneic recipients at this time. In syngeneic recipients, cytokine levels reduced to pretransplant levels by day 13, whereas levels of all cytokines rose after observed rejection onset in the allografts, including TGF-beta1, TGF-beta2, and IL-1RA. The T cell-derived cytokines IL-4, IL-13, and IFN-gamma were detected only during the rejection phase in allogeneic recipients. CONCLUSIONS: There is an early cytokine and chemokine response to the transplantation process, evident in syngeneic and allogeneic grafts, that probably drives angiogenesis, leukocyte recruitment, and affects leukocyte functions. After an immune response has been generated, allogeneic rejection results in the expression of Th1 cytokines (IL-2, IL-12 p40, IFN-gamma), Th2 cytokines (IL-4, IL-6, IL-10, and IL-13), and antiinflammatory/Th3 cytokines (TGF-beta1/2 and IL-1RA).

Gene delivery to the corneal endothelium.

Gene transfer to the corneal endothelium has potential for modulating rejection of corneal grafts. It can also serve as a convenient and useful model for gene therapy of other organs. In this article we review the work carried out in our laboratory using both viral and nonviral vectors to obtain gene expression in the cornea.

Local bioactive tumour necrosis factor (TNF) in corneal allotransplantation.

The aim of this study was to examine the kinetic profile of bioactive TNF levels in aqueous humour of rabbit eyes undergoing corneal allograft rejection and to investigate the effect of locally blocking TNF activity after corneal transplantation. In a rabbit corneal transplantation, endothelial allograft rejection was identified and correlated with increase in central graft thickness. Samples of aqueous humour obtained on alternate days following transplantation were tested for TNF mRNA and bioactive TNF protein. To investigate the effect of locally blocking TNF activity in allograft recipients, the fusion protein TNFR-Ig was administered by injections into the anterior chamber after transplantation. Pulsatile increases in levels of this cytokine were found in 14 of 15 allograft recipients. Peaks of TNF bioactivity preceded by varying intervals the observed onset of rejection in allograft recipients. TNF levels were not elevated in aqueous humour from corneal autograft recipient controls or in serum of allografted animals. mRNA levels were elevated before onset of and during clinically observed allograft rejection. In three of seven animals receiving TNFR-Ig injections on alternate days from day 8 to day 16 post-transplant, clear prolongation of corneal allograft survival was demonstrated. Bioactive TNF is present in aqueous humour following rabbit corneal allotransplantation. Rather than correlating directly with endothelial rejection onset, pulsatile peak levels of TNF precede and follow the observed onset of endothelial rejection. Blockade of TNF activity prolongs corneal allograft survival in some animals, indicating that this cytokine may be a suitable target in local therapy of corneal allograft rejection.

Activated polyamidoamine dendrimers, a non-viral vector for gene transfer to the corneal endothelium.

We investigated the efficiency of activated polyamidoamine dendrimers, a new class of nonviral vectors, to transfect rabbit and human corneas in ex vivo culture. In addition to assessing the expression of a marker gene we have demonstrated that this approach can be used to induce the production of TNF receptor fusion protein (TNFR-Ig), a protein with therapeutic potential. Whole thickness rabbit or human corneas were transfected ex vivo with complexes consisting of dendrimers and plasmids containing lacZ or TNFR-Ig genes. Following optimisation 6-10% of the corneal endothelial cells expressed the marker gene. Expression was restricted to the endothelium and was maximal after transfection with 18:1 (w/w) activated dendrimer:plasmid DNA ratio and culture for 3 days. The supernatant of corneas transfected with TNFR-Ig plasmid contained TNFR-Ig protein which was able to inhibit TNF-mediated cytotoxicity in a bioassay. We have therefore shown that activated dendrimers are an efficient nonviral vector capable of transducing corneal endothelial cells ex vivo. They may have applications in gene-based approaches aimed at prevention of corneal allograft rejection or in treatment of other disorders of corneal endothelium.

Radiofrequency diathermy capsulorhexis of the anterior and posterior capsules in pediatric cataract surgery: preliminary results.

PURPOSE: To assess the effectiveness of radiofrequency diathermy capsulorhexis in preventing opacification of the posterior capsule in pediatric cataract extraction. SETTING: The Children's Hospital, Dublin, Ireland. METHODS: Radiofrequency diathermy capsulorhexis to the anterior capsule followed by injection of sodium hyaluronate behind the posterior capsule and primary posterior capsule diathermy capsulorhexis were performed in 14 eyes of 7 children requiring cataract surgery. RESULTS: Six patients had bilateral congenital and 1 patient bilateral developmental cataracts. Ten eyes (5 patients) received heparin-surface-modified intraocular lenses, and 4 eyes (2 patients) were left aphakic. There were no intraoperative complications, and only mild anterior segment inflammation was noted postoperatively. CONCLUSION: With follow-up from 7 to 16 months (mean 12.1 months), our results showed no epithelial regrowth or opacification of the posterior capsule following diathermy capsulorhexis.