A factor found in the IgG fraction of serum of patients with paraneoplastic bilateral diffuse uveal melanocytic proliferation causes proliferation of cultured human melanocytes.

PURPOSE: To determine if there is a factor in the serum of patients with bilateral diffuse uveal melanocytic proliferation (BDUMP) that causes melanocytic proliferation. METHODS: Human melanocytes and melanoma cells were grown and exposed to serum or plasma of patients with BDUMP, other neoplastic conditions, or control media. Preliminary studies using serum were conducted in an unmasked fashion. In addition, IgG-depleted and IgG-enriched plasma was also tested in a similar fashion. Experiments using plasma were conducted triple masked. To show that the proliferation was melanocyte selective, human dermal fibroblasts, keratinocytes, and ovarian cancer cells were treated with plasma of the BDUMP cases or controls, and the effect of this exposure on their proliferation was quantified. RESULTS: At 72 hours, the serum of BDUMP patients caused statistically significant increased proliferation of normal human melanocytes. Further studies at 6 days demonstrated similar findings. In addition, melanocytes grown in BDUMP serum exhibited a disorganized morphology with foci of multilayered cells. Cultured melanoma cells also showed statistically significant increase in growth in serum from BDUMP patients compared with controls. Masked plasma studies further confirmed these findings and showed that the IgG fraction appeared to contain the melanocyte growth-stimulating factor. The human fibroblasts, keratinocytes, and ovarian cancer cells did not show an increase in growth with the BDUMP plasma treatment. CONCLUSION: Patients with BDUMP have a factor in the IgG fraction that selectively causes melanocyte proliferation. How it causes proliferation of human melanocytes and melanoma cells needs to be further elucidated.

Creation of a drug-coated glaucoma drainage device using polymer technology: in vitro and in vivo studies.

OBJECTIVE: To create and test a slow-release antifibrotic drug-coated glaucoma drainage device using in vitro and in vivo experiments. METHODS: A slow-release device incorporating mitomycin C in poly(2-hydroxyethyl methacrylate) disks was developed using redox-polymerization techniques. A standardized preparation of this drug delivery device was attached to the Ahmed glaucoma valve (model FP7; New World Medical, Inc, Rancho Cucamonga, California). Semicircular disks (5 x 6 mm) of P(HEMA)-mitomycin C containing varying concentrations of mitomycin C per gram dry weight of the gel were attached to the lower half of an Ahmed glaucoma valve plate. Water was pumped through the modified Ahmed glaucoma valve at a rate comparable to that of aqueous humor outflow, and mitomycin C release was measured. Modified and unmodified Ahmed glaucoma valves were implanted in a rabbit model, and drug release and fibrosis were assessed after 3 months. RESULTS: The P(HEMA)-mitomycin C device released mitomycin C in vitro over 1 to 2 weeks. Studies in rabbits revealed that mitomycin C was released from the disks during the 3-month implantation. Histologic analysis demonstrated a significant reduction in inflammatory reaction and fibrosis in the resulting blebs. CONCLUSION: Our slow-release drug-coated glaucoma drainage device decreased fibrosis and inflammation in the resulting bleb in a rabbit model. CLINICAL RELEVANCE: This device could reduce the failure rate of glaucoma drainage devices.

Current trends in age-related macular degeneration.

Age-related macular degeneration is the leading cause of irreversible blindness in older persons of the developed world. Addressing treatable risk factors reduces the incidence and progression of this condition. Recent advances in understanding and treating macular degeneration have dramatically improved the visual prognosis.

Rational use of the fixed combination of dorzolamide - timolol in the management of raised intraocular pressure and glaucoma.

Glaucoma is a multifactorial optic neuropathy in which the main therapeutic target is lowering of intraocular pressure (IOP) in order to retard the progression of existing structural and functional damage. The three mainstays of treatment are pharmacologic, laser, and surgical. The primary standard therapy in patients with open-angle glaucoma or ocular hypertension is topical medication. When monotherapy does not adequately lower the intraocular pressure, one or more agents are added or substituted. Combination pharmacotherapy such as Cosopt((R)) is available to improve efficacy and simplify medication regimen. A fixed combination of two ocular hypotensive drugs (the carbonic anhydrase inhibitor dorzolamide and the beta-adrenoceptor antagonist timolol), Cosopt((R)) is indicated for the treatment of elevated IOP in patients with open-angle glaucoma or ocular hypertension insufficiently responsive to topical beta-adrenoceptor antagonist monotherapy. Compared with concomitant therapy with the individual components, the primary advantage of fixed combination dorzolamide - timolol is convenience, which may also improve compliance. Clinical trials have demonstrated that the fixed combination dorzolamide - timolol is safe, effective and generally well tolerated in lowering IOP in patients with open angle glaucoma or ocular hypertension, including individuals uncontrolled on beta-adrenoceptor antagonist or other monotherapy.