Mitomycin: clinical applications in ophthalmic practice

Mitomycin (mitomycin C; MMC) is an antibiotic isolated from Streptomyces caespitosus. The drug is a bioreductive alkylating agent that undergoes metabolic reductive activation, and has various oxygen tension-dependent cytotoxic effects on cells, including the cross-linking of DNA. It is widely used systemically for the treatment of malignancies, and has gained popularity as topical adjunctive therapy in ocular and adnexal surgery over the past 2 decades. In ophthalmic medicine, it is principally used to inhibit the wound healing response and reduce scarring of surgically fashioned ostia. Hence, it has been used as adjunctive therapy in various ocular surgeries, such as glaucoma filtering surgeries, dacryocystorhinostomy, corneal refractive surgery and surgeries for ocular cicatrisation. In addition, it has been used as an adjunct in the surgical management of pterygia, ocular surface squamous neoplasia, primary acquired melanosis with atypia and conjunctival melanoma. In many of these surgeries and ophthalmic pathologies, MMC showed a significant beneficial effect.     

Heterophils isolated from chickens resistant to extra-intestinal Salmonella enteritidis infection express higher levels of pro-inflammatory cytokine mRNA following infection than heterophils from susceptible chickens

Previous studies showed differences in in vitro heterophil function between parental (A > B) broilers and F1 reciprocal crosses (D > C). Our objectives were to (1) determine if in vitro variations translate to differences in resistance to Salmonella enteritidis (SE) and (2) quantitate cytokine mRNA in heterophils from SE-infected chicks. One-day-old chicks were challenged and organs were cultured for SE. Chicks with efficient heterophils (A and D) were less susceptible to SE compared to chicks with inefficient heterophils (B and C). Heterophils were isolated from SE-infected chicks and cytokine mRNA expression was evaluated using quantitative real-time RT-PCR. Pro-inflammatory cytokine mRNA was up-regulated in heterophils from SE-resistant chicks compared to susceptible chicks. This is the first report to quantitate cytokine mRNA in heterophils from SE-infected chicks. These data show a relationship between in vitro heterophil function, increased pro-inflammatory cytokine mRNA expression, and increased resistance to SE in 1-day-old chicks.     

Comparison of corneal flap thickness between primary and fellow eyes using three microkeratomes

PURPOSE: To compare corneal flap thickness created in laser in situ keratomileusis (LASIK) in primary (right) and fellow (left) eyes (same blade for both eyes) using three microkeratomes. METHODS: The corneal thickness of 132 eyes (66 patients) was measured preoperatively and intraoperatively after flap creation. Corneal flap thickness was calculated by subtracting stromal bed thickness from total corneal thickness. Three microkeratomes were used: Nidek MK-2000, Bausch and Lomb Surgical Hansatome, and the Chiron Automated Corneal Shaper (ACS). Each patient had both corneas cut by one microkeratome and one blade at the same session. RESULTS: Mean corneal flap thickness created in primary eyes was 128.30 +/- 12.57 microm (range 105 to 147 microm) for the ACS (160-microm plate and 8.5-mm ring) and 122.96 +/- 13.30 microm (range 86 to 140 microm) for fellow eyes; Hansatome (160-microm plate and 8.5-mm ring): 141.16 +/- 20.11 microm (range 101 to 169 microm) in primary eyes and 120.95 +/- 26.95 microm (range 107 to 151 microm) in fellow eyes; Nidek (130-microm plate and 8.5-mm ring): 127.25 +/- 4.12 microm (range 116 to 134 microm) in primary eyes and 127.54 +/- 3.7 microm (range 119 to 134 microm) in fellow eyes. The corneal flap in the ACS and Hansatome microkeratomes was always thicker in the primary than the fellow eye, using the same blade for both eyes. No significant difference was found using the Nidek microkeratome. CONCLUSION: Corneal flap thickness tended to be thinner in fellow eyes than in primary eyes for the ACS and Hanstome microkeratomes. The Nidek microkeratome results were closer to specified corneal flap thickness than the ACS and Hanstome microkeratomes.     

The immunomodulator vasoactive intestinal peptide (VIP) does not affect experimental autoimmune uveitis (EAU) in B10.RIII mice

PURPOSE: Vasoactive intestinal peptide (VIP) exhibits immunomodulatory activities both in vivo and in vitro, including efficient inhibition of murine experimental arthritis. In this study, we investigated the effects of VIP treatment on the induction of experimental autoimmune uveoretinitis (EAU). METHODS: EAU was induced in B10.RIII mice by immunization with interphotoreceptor retinoid-binding protein (IRBP) using routine methods, but without treatment with pertussis toxin (PTX). VIP was injected i.p. at different doses into mice on alternate days. Mice were tested by conventional methods for ocular inflammation, antibody levels, lymphocyte proliferation, and cytokine release by cultured lymphocytes. RESULTS: Treatment with VIP, at different doses, had essentially no effect on the development of EAU or antibody production in the B10.RIII mice. The treatment did have variable effects on the low interferon-gamma production by lymphocytes of these mice. CONCLUSION: Unlike its inhibitory effect in the experimental arthritis system, VIP did not modulate the development of EAU in B10.RIII mice.     

C-reactive protein levels in normal tension glaucoma

PURPOSE: To determine C-reactive protein (CRP) levels in patients with normal tension glaucoma (NTG). METHODS: This study included 20 cases with NTG and 30 controls, with no history of ocular disease. Plasma CRP levels of all the study participants were determined using a highly sensitive CRP kit. RESULTS: Twenty cases (11 males, 9 females, mean age 69 +/- 5 years) with NTG and 30 age-matched controls (15 males, 15 females, mean age 68 +/- 6) were evaluated. Both groups had similar demographic parameters (age, sex, BMI). Plasma CRP levels were significantly higher in the NTG cases than in controls (median [range], 3.20 [0.17-8.4] mg/dL compared with 0.5 [0.1-3.2], P < 0.001). The mean plasma CRP level was significantly elevated in the NTG cases compared with the controls (3.21 +/- 0.6 mg/dL and 0.85 +/- 0.17 mg/dL, respectively, P < 0 0.01). CONCLUSION: Our findings suggest that higher CRP levels may be associated with NTG. It is possible that a vascular inflammatory process is involved in the etiology of this glaucoma.     

Ophthalmic manifestations of multiple myeloma

PURPOSE: To describe ophthalmic manifestations in a series of patients with multiple myeloma (MM) and review the literature. DESIGN: Retrospective case series. METHODS: Review of all cases with ophthalmic manifestations of MM seen at the Department of Ophthalmology, Royal Adelaide Hospital, between 1987 and 2002. RESULTS: Of all patients with MM who were managed at the Royal Adelaide Hospital in the study period, only 8 were referred to the Ophthalmology Department with ophthalmic manifestations. Five males and 3 females with a mean age of 61.25 years (range 42-78) who exhibited ophthalmic manifestations were studied. Six patients (75%) had known MM at the time of their ophthalmic evaluation. Four patients (50%) had neuro-ophthalmic symptoms resulting in diplopia or visual disturbances. Three patients (37.5%) presented with orbital involvement and 1 (12.5%) with hyperviscosity retinopathy. Five patients (62.5%) died within 2 months of their ophthalmic presentation. CONCLUSION: Ophthalmic manifestations of MM are uncommon and diverse. They may appear at the initial presentation of the disease or occur late in the disease process. Awareness of the possible manifestations may lead to an earlier diagnosis and have a positive influence on the disease course.     

Factor VIII efficient and specific non-covalent binding to PEGylated liposomes enables prolongation of its circulation time and haemostatic efficacy

Haemophilia A is a bleeding disorder caused by the lack of factor VIII (FVIII). We report the prolongation of exogenous FVIII circulation time and haemostatic efficacy by its formulation with PEGylated liposomes (PEGLip). FVIII binds non-covalently but with high affinity in a specific mode with the external surface of PEGLip neither losing its activity nor its binding to von Willebrand Factor. Experiments in haemophilic and non-haemophilic mice indicate that the circulation time and clotting efficacy of PEGLip-formulated exogenous FVIII (PEGLip-FVIII) are significantly enhanced over those of free FVIII. The data support the feasibility of using PEGLip-FVIII to extend the duration of haemostatic efficacy in the treatment of haemophilia A.     

Atrial septal perforation from TIPS stent migration

Transjugular intrahepatic portosystemic shunts (TIPS) are safe and effective for the treatment of portal hypertension. Cardiac complications are unusual. This study reports a case of TIPS stent migration to the right atrium causing perforation of the atrial septum in a patient with end-stage liver disease. The shunt was removed transvenously but attempts at transvenous occlusion of the septal perforation were unsuccessful. The patient went on to undergo combined open-heart surgery with septum repair and liver transplantation. The case highlights a rare complication of TIPS and methods for treatment including transvenous removal, transvenous repair, and combined cardiotomy-liver transplantation surgery.