Performance profile of sodium hyaluronate in patients with lipid tear deficiency: randomised, double-blind, controlled, exploratory study.

AIM: To assess the short-term efficacy of hypotonic 0.18% sodium hyaluronate in patients with evaporative tear-sufficient dry eye due to lipid tear deficiency (LTD). METHODS: This was a randomised, double-blind, controlled, exploratory study. A total of 10 patients with dry eye due to LTD were treated as follows: one drop of hypotonic 0.18% sodium hyaluronate in one eye and one drop of isotonic 0.3% hydroxypropyl-methylcellulose (HPMC)/0.1% dextran in the other eye. Non-invasive tear film break-up time (NIBUT) evaluated by using a tear scope with grid pattern and subjective ocular symptoms of dry eye were assessed at 15, 30, 60 and 90 min after instillation. RESULTS: Both sodium hyaluronate and HPMC/dextran caused a significant (p<0.05) improvement in NIBUT and symptoms. Mean (SD) NIBUT in the sodium hyaluronate group was 3.2 (1.0), 6.4 (2.8), 5.5 (1.9), 5.3 (1.3) and 3.9 (1.7) s at 0, 15, 30, 60 and 90 min, respectively, compared with 3.6 (1.9), 5.5 (3.2), 5.0 (1.5), 4.4 (2.2) and 3.5 (1.2) s in the HPMC/dextran group. However, increase in NIBUT was significantly (p<0.05) greater and longer in the sodium hyaluronate group than in the HPMC/dextran group. CONCLUSION: Treatment with sodium hyaluronate and HPMC/dextran eye drops is useful for treating patients with dry eye due to LTD. However, sodium hyaluronate caused a significantly (p<0.05) greater increase in NIBUT values than HPMC/dextran in such patients.

Single and multilayer amniotic membrane transplantation for persistent corneal epithelial defect with and without stromal thinning and perforation.

AIMS: To evaluate the efficacy of amniotic membrane transplantation (AMT) in persistent corneal epithelial defect with or without stromal thinning and corneal perforation. METHODS: 28 patients (28 eyes) with persistent corneal epithelial defect unresponsive to medical treatment were given preserved human amniotic membrane transplants. The patients were divided into three groups: group A, persistent corneal epithelial defect 10 eyes; group B, epithelial defect with stromal thinning 13 eyes; and group C, corneal perforation five eyes. AMT was performed using one layer in group A and multilayers in group B and C. The causes of persistent epithelial defect were neurotrophic keratopathy (24 eyes), limbal deficiency (six eyes), exposure keratopathy (four eyes), and Mooren's ulcer (one eye). RESULTS: Success was noted in 82.1% (23/28 eyes) in all groups, with 80% (8/10 eyes), 84.6% (11/13 eyes), and 80% (4/5 eyes) in groups A, B, and C respectively, with a mean follow up of 10.9 months (1-30 months). The mean epithelialisation time after AMT was 2.1 weeks. The healing times of groups B and C are also significantly shorter than group A (p=0.017 and 0.018, respectively). Corneal stromal thickness was significantly increased in all cases in groups B and C (p=0.006). Those with corneal perforation in group C were completely healed by multilayer AMT. There was no difference in the epithelialisation time between successful cases treated by a single operation (17 eyes) or repeated operation (six eyes). Vision improved in 18.9% (8/28 eyes) and worsened as a result of cataract formation in 2.3% (1/28 eyes). Failure was noted in 17.9% (5/28 eyes), because of corneal infection (two eyes), neurotrophic keratopathy with and without limbal deficiency (two eyes), and intractable corneal perforation (one eye). No patient developed major immediate postoperative complications or graft rejection. CONCLUSION: Amniotic membrane can successfully treat refractory corneal epithelial defect by promoting epithelial healing and thus prevent corneal perforation. It can be used as a treatment for corneal perforation by restoring corneal stromal thickness so that emergency penetrating keratoplasty can be avoided.

Intraocular lens removal from [corrected] patients with uveitis.

PURPOSE: To report a series of patients with uveitis and cataract who had undergone cataract extraction with posterior chamber intraocular lens implantation and who subsequently had the intraocular lens removed because of progressive intraocular damage from inflammation. METHODS: Review of the records of 19 patients after removal of a posterior chamber intraocular lens. The decision to perform surgery was based on standard criteria after evaluation at a single uveitis referral center. RESULTS: The complications leading to intraocular lens removal were perilental membrane (eight eyes), chronic low-grade inflammation not responding to anti-inflammatory treatment (eight eyes), and cyclitic membrane resulting in hypotony and maculopathy (three eyes). After intraocular lens removal the inflammation subsided and the visual acuity improved or stabilized in 14 of the 19 eyes. The causes of further reduction in the visual acuity of the other five patients were macular edema (two patients), maculopathy resulting from hypotony (one patient), retinal detachment (one patient), and vitreous hemorrhage (one patient). CONCLUSIONS: Intraocular lens implantation can form part of a reasonable plan for visual rehabilitation of patients with uveitic cataract, but inclusion of an intraocular lens in the plan is not always in the overall long-term best interest of the patient. Intraocular lens removal may salvage useful vision for patients who continue to exhibit complications secondary to uveitis after cataract extraction and intraocular lens implantation, provided the intraocular lens is removed before irreparable damage has been done to macula or optic nerve.

The role of antibody to human beta4 integrin in conjunctival basement membrane separation: possible in vitro model for ocular cicatricial pemphigoid.

PURPOSE: To demonstrate the specific binding of autoantibodies present in the sera of patients with ocular cicatricial pemphigoid (OCP) to human beta4 integrin present in the normal human conjunctiva (NHC) and to study the role of OCP autoantibodies and antibody to human beta4 integrin in the pathogenesis of subepithelial lesion formation in OCP. METHODS: Indirect immunofluorescence assay and in vitro organ culture method using NHC were used. Sera and IgG fractions from 10 patients with OCP; immunoaffinity-purified OCP autoantibody; antibodies to human beta4, beta1, alpha6, and alpha5 integrins; and sera from patients with pemphigus vulgaris, bullous pemphigoid (BP), and chronic atopic and chronic ocular rosacea cicatrizing conjunctivitis; and normal human serum (NHS) were used. RESULTS: Nine of 10 OCP sera or IgG fractions, immunoaffinity-purified OCP autoantibody, antibodies to human beta4 and alpha6 integrins, and sera from patients with BP showed homogenous, smooth linear binding along the basement membrane zone (BMZ) of the NHC. NHS, antibodies to other integrins, and sera from patients with chronic cicatrizing conjunctivitis from other causes showed no such binding. When NHC was first absorbed with OCP sera and then reacted with anti-beta4 antibodies or vice versa, the intensity of the BMZ binding was dramatically reduced or completely eliminated, indicating that there were autoantibodies in OCP sera specific for the beta4 integrin. BMZ separation developed 48 to 72 hours after addition of total OCP sera, IgG fractions from OCP sera, immunoaffinity-purified autoantibodies from sera of patients with OCP, or anti-beta4 antibodies to the NHC cultures, but not after addition of normal control sera, sera from patients with chronic cicatrizing conjunctivitis from causes other than OCP, or sera from patients with OCP in clinical remission. CONCLUSION: Circulating anti-beta4 integrin antibody may have an important role in the pathogenesis of OCP.

The use of topical cyclosporin A in ocular graft-versus-host-disease.

Ocular manifestations of GVHD include keratoconjunctivitis sicca, cicatricial lagophthalmos, sterile conjunctivitis, persistent corneal epithelial defects, corneal ulcers and corneal melting. Conventional initial therapy such as lubrication and topical steroids is directed to treat decreased tear production and ocular surface abnormalities. The purpose of this study was to illustrate the possible benefit of topical cyclosporin A 1% (CsA) as an adjunct in managing ocular surface abnormalities in five cases of GVHD refractory to conventional therapy. Five clinical case reports of chronic GVHD patients in whom conventional therapy was inadequate to stop the progression from its initial presentation are described. Patient presentation varied in severity on a spectrum of mild to moderate diffuse punctate epithelial erosions to sterile necrotizing corneal melts. Although systemic therapy for GVHD consisting of systemic immunosuppressants (ie cyclosporin A and corticosteroids) was given to these patients, this therapy was insufficient in managing the ocular manifestations of the disease. Topical CsA was added to the treatment regimen and the progression of the ocular disease was recorded. The addition of topical CsA 1% probably helped in controlling the epithelial keratitis and melting process in our reported cases and we conclude that topical CsA may be an appropriate modality in managing ocular surface abnormalities in patients with ocular GVHD after conventional treatments have been tried. However, a further randomized clinical prospective study is needed to evaluate the efficacy of topical CsA in managing these problems in GVHD patients.

Costimulatory molecules in ocular cicatricial pemphigoid.

PURPOSE: To examine normal and inflamed conjunctiva from patients with ocular cicatricial pemphigoid (OCP) for the presence of costimulatory molecule CD28 and its ligands B7-1 (CD80) and B7-2 (CD86). METHODS: Conjunctival biopsy specimens from 12 patients with OCP and from five healthy persons undergoing cataract surgery were analyzed by light microscopy and immunohistochemical examination with monoclonal antibody probes for CD28, B7-1, and B7-2 molecules and for mononuclear cell subtypes. RESULTS: Epithelium of OCP conjunctiva showed more Langerhans' cells, B7-1-positive (+) cells, and B7-2 expression (ratio of B7-2-positive cells to antigen-presenting cells). In the substantia propria, OCP specimens showed significantly increased numbers of T cells (CD3 +), macrophages (CD68+), CD28+ cells, B7-2+ cells (CD86+), Langerhans' cells (CD1a), and B7-1+ cells (CD80). Most of the B7-2+ cells, macrophages, and Langerhans' cells were located subepithelially. B7-2 expression was significantly higher in OCP conjunctival substantia propria compared with normal conjunctiva. CONCLUSIONS: The results of this study indicate that the expression of the costimulatory molecule B7-2 is upregulated in conjunctiva of patients with active OCP. This increased subepithelial B7-2 expression may contribute to the sustained immune activation in OCP conjunctiva.