Pharmacologic therapy of mycotic keratitis

Mycotic keratitis continues to be an important cause of corneal blindness, especially in tropical and subtropical countries. The prognosis is poor compared with many other forms of keratitis because of the lack of effective antifungal drugs. The currently available antifungal drugs suffer from multiple drawbacks such as poor ocular penetration, unpredictable bioavailability, and adverse effects associated with systemic medications. Over the last decade, several new drugs and drug-delivery systems have been introduced in an attempt to improve the treatment outcomes. Thorough knowledge of the currently available antifungal drugs, their spectrum of action, and associated adverse effects is essential to deal with cases of mycotic keratitis. We discuss the pharmacologic properties and clinical use of the currently available antifungal drugs.     

Slit-lamp needle revision of failed filtering blebs using high-dose mitomycin C

PURPOSE: To investigate the efficacy of bleb needle revision with high-dose mitomycin C in reviving failed filtering blebs after 1 year. PATIENTS AND METHODS: We reviewed the charts of 44 patients with one eye that had undergone bleb needle revision with a mixture of 0.1 mL of mitomycin (0.4 mg/mL) mixed with 0.1 mL of non-preserved 1% lidocaine. At least 12 months of follow-up were required. A successful bleb needle revision was defined as one that did not require a subsequent needling, glaucoma surgery, or medication to reach an intraocular pressure (IOP) greater than 4 mm Hg but less than 22 mm Hg. A qualified success was defined as a successful bleb needle revision that required subsequent needling or medication. RESULTS: The bleb needle revision with high-dose mitomycin was a success or qualified success after 12 months in 28 patients or 64% (95% confidence interval, 50% to 78%). The baseline IOP in these patients was 26.7 +/- 8.2 mm Hg (range 15 to 48 mm Hg) using an average of 1.5 +/- 1.5 glaucoma medications. The IOP after 1 year was 13.6 +/- 4.0 (range 6 to 21 mm Hg) with an average of 0.5 +/- 0.8 medications. Of 44 patients, 17 (39%) were successes and 11 (25%) were qualified successes. CONCLUSION: Bleb needle revision with high-dose MMC was effective in reducing the IOP in 64% of eyes with a failed filtering bleb with minimal long-term complications.     

Deep anterior lamellar keratoplasty combined with autologous limbal stem cell transplantation in unilateral severe chemical injury

PURPOSE: To evaluate the efficacy of deep anterior lamellar keratoplasty combined with autologous limbal stem cell transplantation for ocular surface reconstruction and visual rehabilitation in eyes with unilateral, late-stage, severe chemical injury. METHODS: This was a retrospective, noncomparative, interventional case series that included 7 eyes of 7 patients, with severe unilateral late stage chemical injury, exhibiting corneal vascularization, conjunctivalization, and extensive corneal scarring were treated at the C. J. Shah Cornea Service, Sankara Nethralaya, a tertiary care center. Surgical procedures included releasing symblepharon adhesions, excising epibulbar fibrous tissue, superficial keratectomy to remove fibrovascular tissues over cornea, deep anterior lamellar dissection, grafting a lamellar corneal button, and transplanting autologous limbal graft, with or without amniotic membrane transplantation. The main outcome measures were relief of patient symptoms, postoperative recovery of the ocular surface, corneal clarity, corneal epithelial stability, and best corrected visual acuity. RESULTS: The mean duration between the injury and surgery was 24.4 +/- 21.8 months. No intraoperative complications were noted. Successful epithelialization was achieved in all eyes. The reconstructed corneal surface remained stable during the entire follow-up period (mean follow-up, 16.57 +/- 5.12 months). All patients had resolution of ocular symptoms. Remarkable improvement in vision was noted in all (85.7%) except 1 eye in which recovery was limited due to amblyopia. The average best corrected visual acuity at last follow-up was 20/50. No complications were noted in the donor fellow eye. CONCLUSIONS: DALK combined with autologous limbal transplantation can restore a healthy, stable ocular surface, besides providing a clear cornea that remarkably improves the visual acuity, in patients with unilateral, late stage, severe chemical injury.     

Picroliv accelerates epithelialization and angiogenesis in rat wounds

Tissue repair and wound healing are complex processes that involve inflammation, granulation and tissue remodeling. Angiogenesis plays a central role in wound healing. Earlier, we have shown that picroliv, a natural product obtained from the roots of Picrorhiza kurrooa, up-regulates the expression of vascular endothelial growth factor in human umbilical vein endothelial cells and of insulin-like growth factor in rats during hypoxia. In the present study, we have investigated the effect of picroliv in an ex vivo rat aorta ring model of angiogenesis. Picroliv enhanced the sprouting and migration of endothelial cells. We also investigated punch wound healing on days 4 and 7 after wounding by histology, morphometry and collagenization. The data showed improved re-epithelialization, neovascularization and migration of various cells such as endothelial, dermal myofibroblasts and fibroblasts into the wound bed after picroliv treatment. Immunohistochemical localization showed increased VEGF and alpha smooth muscle actin staining consistent with an increased number of microvessels in granulation tissue. These findings suggest that picroliv could be developed as a therapeutic angiogenic agent for the restoration of the blood supply in diseases involving inadequate blood supply such as limb ischemia, ischemic myocardium and wound healing.     

Characterizing pseudoexfoliation syndrome through the use of ultrasound biomicroscopy

PURPOSE: To determine the clinical utility of ultrasound biomicroscopy (UBM) in diagnosis of pseudoexfoliation (PEX) syndrome by characterizing the lens capsule and zonules before cataract surgery. SETTING: Veterans Administration Hospital, East Orange, and University of Medicine & Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey, USA. METHODS: Ultrasound biomicroscopy was performed on 10 patients clinically diagnosed with PEX syndrome. The clinical diagnosis was made by the presence of fibrillin deposits on the anterior lens capsule, lack of pigment at the pupillary ruff, and poor pharmacologic dilation. Five persons without PEX were used as controls. The thickness of the anterior lens capsule was measured in 5 locations in each eye: centrally and in the peripheral lens capsule superiorly, inferiorly, nasally, and temporally. Four measurements were taken from the zonule at the thickest point on each fiber. The UBM also found the presence or absence of nodular deposits on the zonules. RESULTS: The anterior and peripheral lens capsule in patients with PEX was thicker than that in the control group. Additionally, patients with PEX had thicker zonules than the control group and had nodular deposits present; the control group had no deposits. These differences were all significant with a 99% confidence interval. CONCLUSIONS: A thicker anterior lens capsule and lens zonule nodules were associated with PEX. These abnormalities can be visualized with the UBM to confirm the diagnosis of PEX and identify patients at risk for operative complications.     

Retreatment of LASIK

PURPOSE: To review the indications, techniques, and results of retreatment LASIK. METHODS: Review of the literature and the authors' experience. RESULTS: Patient selection is the key to successful LASIK enhancement. The enhancement procedure should generally be undertaken 3 months after the initial LASIK procedure. Relifting of the flap may be done easily within 1 year of previous LASIK surgery. A new LASIK flap is required in cases with previously complicated LASIK. LASIK retreatment by lifting the flap is an effective and safe procedure. Overall improvement is seen in uncorrected visual acuity (> or = 20/20 and > or = 20/40) and postoperative spherical equivalent refraction within +/- 0.5 D and +/- 1.0 D. CONCLUSIONS: LASIK retreatment is an effective modality to treat regressions and residual refractive errors.     

Isolation and characterization of degradation impurities in docetaxel drug substance and its formulation

The degradation of docetaxel drug substance and its injection formulation has been investigated. The majority of impurities were observed in a base degradation study and all five degradation products were characterized. These impurities were isolated, enriched and were subjected to mass and NMR spectral studies. Based on the spectral data, these were characterized as 10-deacetyl baccatin III, 7-epi-10-deacetyl baccatin III, 7-epi-10-oxo-10-deacetyl baccatin III, 7-epi docetaxel and 7-epi-10-oxo-docetaxel, respectively. The last two impurities were also detected in the stability study of docetaxel formulation. Out of these degradation impurities two substances have been previously identified while the other three previously unreported.     

Effect of the melt granulation technique on the dissolution characteristics of griseofulvin

This work describes a melt granulation technique to improve the dissolution characteristics of a poorly water-soluble drug, griseofulvin. Melt granulation technique is a process by which pharmaceutical powders are efficiently agglomerated by a meltable binder. The advantage of this technique compared to a conventional granulation is that no water or organic solvents is needed. Because there is no drying step, the process is less time consuming and uses less energy than wet granulation. Granules were prepared in a lab scale high shear mixer, using a jacket temperature of 60 degrees C and an impeller speed of approximately 20,000 rpm. The effect of drug loading (2.5/5%), binder (PEG 3350/Gelucire 44/14), filler (starch/lactose), and HPMC on the dissolution of griseofulvin was investigated using a half two level-four factor factorial design. The granules were characterized using powder XRD, DSC and SEM techniques. A significant enhancement in the in vitro dissolution profiles of the granules was observed compared to the pure drug and drug excipient physical mixtures. The factorial design results indicated that higher drug loading and the presence of HPMC reduced the extent of dissolution of the drug, whereas, the presence of starch enhanced the dissolution rate. XRD data confirmed crystalline drug in formulation matrices. DSC results indicated monotectic mixtures of griseofulvin with PEG in the granulated formulations. In conclusion, the results of this work suggest that melt granulation is a useful technique to enhance the dissolution rate of poorly water-soluble drugs, such as, griseofulvin.     

Outcomes associated with the use of biologic agents in moderate to severe psoriasis

An estimated 2.1% of Americans have psoriasis and approximately 30% of them have moderate to severe psoriasis. Although the disease is not associated with mortality, it has a significant impact on health-related quality of life among patients. Several therapies are available for psoriasis including topical agents, phototherapy, and systemic medications. Recently, effective yet expensive biologic agents have been added as treatments for moderate to severe psoriasis. Biologics are recommended in patients for whom all other available treatment options have failed. This extensive review provides important information on the clinical and patient-related outcomes associated with the biologic agents used in psoriasis.     

Synthesis, antiviral, antituberculostic, and antibacterial activities of some novel, 4-(4-substituted phenyl)-6-(4-nitrophenyl)-2-(substituted imino)pyrimidines

A variety of novel 4-(4-substituted phenyl)-6-(4-nitrophenyl)-2-substituted imino) pyrimidines were synthesized by reacting 4-(4-substituted phenyl)-6-(4-nitrophenyl)-2-amino pyrimidines with different substituted aromatic aldehydes, coumarin chloroisatin. The 4-(4-substituted phenyl)-6-(4-nitrophenyl)-2-amino pyrimidines were synthesized by reacting 3-(4'-substituted phenyl)-1-(4-nitrophenyl)-2-propen-1-ones with guanine hydrochloride. 3-(4-Substituted phenyl)-1-(4-nitrophenyl)-2-propen-1-ones were synthesized by reacting 4-nitroacetophenone with different para-substituted aromatic aldehydes. Spectral data (IR, NMR, and mass spectra) confirmed the structures of the synthesized compounds. The synthesized compounds were investigated for their antiviral, antituberculostic, and antibacterial activities. The results of antiviral, antituberculostic, and antibacterial activities indicated that the synthesized compounds exhibited mild to potent activities compared to the respective reference standards.