Infliximab in the treatment of refractory posterior uveitis

PURPOSE: To determine the efficacy and safety of infliximab in the treatment of refractory posterior uveitis. DESIGN: Noncomparative interventional case series. PARTICIPANTS: Five patients with posterior uveitis were treated: 3 had Beh?et's syndrome, and 2 had idiopathic posterior uveitis. INTERVENTIONS: Patients with sight-threatening uveitis refractory to other immunosuppressive agents were treated with infliximab. MAIN OUTCOME MEASURES: Intraocular inflammation, by using binocular indirect ophthalmoscopy score, retinal vasculitis, and visual acuity. Adverse effects of infliximab were documented. RESULTS: Within 2 weeks of the first infusion of infliximab, 4 of 5 patients showed marked improvement in vitreous haze and visual acuity. By the 6-month follow-up, the same four patients had achieved remission of posterior uveitis and had successfully withdrawn all other immunosuppressive therapy. Further infusions of infliximab were required in 3 patients. One patient developed ocular and systemic tuberculosis, which responded to antituberculous treatment. CONCLUSIONS: Infliximab is effective in the treatment of sight-threatening refractory posterior uveitis. However, patients should be thoroughly screened for tuberculosis before treatment and followed up closely during and after therapy with infliximab.     

Laser conjunctivoplasty: a new technique for correction of mild medial ectropion

Thirty patients with mild medial ectropion of the lower lid were treated by Argon green laser. A diamond-shaped area (6 x 4 mm in size) on the medial part of the tarsal conjunctiva of the lower lid was burnt with overlapping spots until white blanching and visible contraction of tissue were seen. The apex of the diamond was kept 4 mm below the punctal opening. After an average follow-up of 6 months, functional success was achieved in 22/30 eyes. Anatomical success in terms of repositioning of the punctum was attained in 24/30 eyes. The only side effect noted was a mild burning sensation of the eyes lasting for two hours after the procedure. This is the authors' initial experience with a somewhat new and easy procedure to treat mild medial ectropion of the lower lid that can be performed on an outpatient basis.     

Stem cell differentiation and the effects of deficiency

Stem cells have several unique attributes, the key features being their potency and plasticity. They have the ability to give rise to multiple cell lineages and to transdifferentiate into totally different cell type(s) when relocated to a novel stem cell niche. Most self-renewing tissues are served by stem cells. At the ocular surface, the corneo-scleral limbus is believed to provide the niche for corneal epithelial stem cells. A large body of circumstantial evidence, both clinical and basic, supports this view. However, specific identification of limbal stem cells has proved elusive. Cytokeratin markers, vimentin, epidermal growth factor receptors, p63, and others have been used to identify epithelial cell populations at the limbus, which could harbour putative stem cells. In contrast, none of the known haematopoietic stem cell markers namely, CD34 and CD133, stain any specific subset of corneal or limbal epithelial cells. Singly or collectively, none of these markers point to any unique cell(s) that could be regarded as stem cells, supporting the notion that the corneal epithelium is served by 'committed progenitors' rather than by stem cells. Disease or destruction of the corneo-scleral limbus is associated with consequential events that eventually lead to visual impairment or blindness. Conjunctivalisation and vascularisation of the corneal surface and persistent or recurring epithelial defects are hallmarks of limbal deficiency.     

Effect of ABO blood group mismatching on corneal epithelial cells: an in vitro study

AIM: To determine, in vitro, the effects of blood group ABO mismatching on corneal epithelial cells. METHODS: Corneal epithelial cell cultures were established from 32 human cadaver donor eyes. Epithelial cells (100 microl of 4 x 10(2) cells per microl) were incubated for 4 hours with antibodies against blood group antigens A, B, and AB, with and without complement. Cell lysis was assayed by a chemiluminescent assay using Cytolite reagent. Live cells, remaining after incubation, were counted in a scintillation counter. The blood group of the donors was determined retrospectively, in a blinded manner. RESULTS: Retrospective tracing of donor blood groups was possible for 20 donors. In all cases the blood group corresponded with that suggested by the cell lysis assay. Significant cell lysis was observed when known A group cells were incubated with anti-A and anti-AB antibody, B group cells were incubated with anti-B and AB antibody, and AB group cells were incubated with anti-AB antibody. Lysis occurred only in the presence of complement. No lysis of O group cells was observed with any of the antibodies. In all cases, lysis was observed only with neat (serum) antibody concentrations. CONCLUSIONS: Blood group ABO mismatching results in significant lysis of corneal epithelial cells. The antibody concentration required for lysis equals that found in serum. Such levels of antibody are unlikely to be achieved in tears and/or aqueous. This may offer an explanation for the conflicting reports of the studies on the effect of blood group matching on corneal grafts. The variability in the outcome may reflect the levels of antibodies gaining access to the corneal cells and not the mismatching alone.     

Ocular surface reconstruction in LOGIC syndrome by amniotic membrane transplantation

PURPOSE: To determine whether preserved amniotic membrane can be used to reconstruct the ocular surface after excision of the invading granulation material typical of LOGIC syndrome (laryngeal and ocular granulation tissue in children from the Indian subcontinent). METHODS: Granulation tissue was dissected and excised from both eyes of a 10-year-old boy with LOGIC syndrome. This procedure was followed by coverage of the corneal, scleral, and subtarsal regions of each eye with amniotic membrane, which had been stored for 6 months at -70 degrees C. RESULTS: Initial 2.5-month follow up demonstrated complete disappearance of granulation tissue. The fornices were patent, there was no recurrence of symblepharon, ocular inflammation was suppressed, and the patient reported markedly increased comfort. Both eyelids remained ptotic because of levator muscle atrophy secondary to many years of inability to open either eye. No residual scarring or evidence of granulation tissue was observed in that period. The 10-month follow up demonstrated limited recurrence, particularly where there was an intraoperative break in the amniotic membrane. CONCLUSIONS: After 24 operations to treat the ocular complications induced by LOGIC syndrome, amniotic membrane transplantation was the first effective treatment. In the early follow up period (2-3 months), there was complete cessation of the proliferation of granulation tissue and reepithelialization of the corneal surface. Longer follow up (10 months) demonstrated limited recurrence, which will require retreatment.     

Aluminium phosphide exposure: implications on rat brain lipid peroxidation and antioxidant defence system

We investigated the effect of aluminium phosphide exposure (10 mg/kg body weight) on lipid peroxidation and antioxidant defence system in different regions of rat brain. A significant increase in lipid peroxidation in cerebrum, cerebellum and brain stem was observed in aluminium phosphide-exposed rats, which was accompanied by a marked decrease in the activities of antioxidant enzyme, superoxide dismutase and catalase. A decline in the activity of glutathione reductase was also observed, however, no change was seen in the activity of glutathione peroxidase following aluminium phosphide administration. Decreased levels of non-protein thiols and total sulfhydryl groups were also observed after aluminium phosphide treatment. It seems evident that aluminium phosphide exposure significantly enhanced neuronal lipoperoxidative damage with concomitant alterations in the antioxidant defence status thus having serious bearing on the functional and structural status of the central nervous system.     

Glioblastoma multiformis, rapidity of growth--importance of repeat CT scan

A case of glioblastoma multiformis (GBM) where lesion appeared within a month of normal CT scan is reported. It emphasises the importance of early CT scan after neurological deterioration particularly in older patients because of rapid growth of glioblastoma.     

Selective delivery of herpes virus vectors to experimental brain tumors using RMP-7

RMP-7, a bradykinin analog, has been shown to selectively open the blood-tumor barrier for the delivery of chemotherapeutic drugs to brain tumors. In contrast to bradykinin, RMP-7 has no hypotensive effects and has been approved for human use. This study was initiated to determine whether RMP-7 would open the blood-tumor barrier to virus vectors encoding tumor-killing genes in an experimental model. The herpes virus vector used, hrR3, which encodes virus thymidine kinase gene and the lacZ reporter gene, is defective in a gene encoding ribonucleotide reductase, replicates selectively in dividing tumor cells and not in postmitotic neural cells. It was determined that an optimum dose of RMP-7 (1.5-3.0 microg/kg over 10-15 minutes) enhanced viral delivery to brain tumors in rats bearing intracranial 9 L gliosarcomas when infused through the carotid artery immediately prior to virus vector application. Maximum expression of the lacZ reporter gene occurred at 3 days after intracarotid infusion. By 8 days, transgene expression was largely confined to tumor foci away from the main tumor mass. Viral delivery was essentially specific to tumor cells, with little transgene expression elsewhere in the brain. Minimal uptake and pathology was noted in the kidney, spleen, and liver. These findings indicate that intracarotid delivery of RMP-7 can augment the selective delivery of virus vectors to brain tumors in an experimental rat model, with the potential for application to human brain tumors.