Effects of Lidocaine on Mitomycin C Cytotoxicity.

PURPOSE: Intra-Tenon or subconjunctival injection of a solution of mitomycin C (MMC) and 1% preservative-free lidocaine (as an anesthetic) has gained popularity for its use in trabeculectomy, a filtering surgery for glaucoma. To our knowledge, no studies have analyzed the impact of lidocaine on the cytotoxic effects of MMC in this setting. This study was conducted to evaluate in vitro fibroblast cytotoxicity to a solution of MMC (0.2 mg/ml) and 1% preservative-free lidocaine. DESIGN: Experimental study. PARTICIPANTS: Nonhuman subject research. METHODS: Cultured human conjunctival fibroblasts were incubated in phosphate-buffered saline (PBS) (control), MMC (0.2 mg/ml), a mixture of 0.2 mg/ml MMC + 1% preservative-free lidocaine, or 1% preservative-free lidocaine. Samples were taken at 2, 5, 10, 30, and 60 minutes, and a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay with photoabsorbance testing was used to assess conjunctival cell viability. MAIN OUTCOME MEASURE: Mean photoabsorbance. RESULTS: Mean photoabsorbance across all time intervals was 0.680 for solutions incubated in PBS, 0.642 for MMC, 0.612 for MMC + 1% preservative-free lidocaine, and 0.605 for 1% preservative-free lidocaine. A 2-way analysis of variance analyzing solution, time, and solution-time interaction on photoabsorbance showed that PBS was least cytotoxic and an optimal control for this study. Tukey post hoc comparisons showed that MMC was more cytotoxic than PBS (P < 0.001). However, both MMC + 1% preservative-free lidocaine and 1% preservative-free lidocaine were more cytotoxic than MMC and PBS (P < 0.01 for all). No significant differences in cytotoxicity comparing lidocaine-containing solutions were observed. CONCLUSIONS: In this in vitro study, we found an increase in cytotoxicity when MMC (0.2 mg/ml) was combined with 1% preservative-free lidocaine. We note that lidocaine did not inhibit MMC cytotoxicity and exhibited a significant cytotoxic effect on its own.

Corneal hysteresis in post-radial keratotomy primary open-angle glaucoma.

PURPOSE: Corneal hysteresis (CH) is a corneal biomechanical property measured by the ocular response analyzer (ORA). It is associated with primary open-angle glaucoma development, progression, and severity as well as intraocular pressure (IOP) measurement. Decreases in CH and changes in IOP measurements have been described for laser-assisted refractive surgery; however, patients with prior radial keratotomy (RK) have not been examined. We have performed a cohort study examining CH and intraocular pressure measurements (Goldmann applanation and ORA values including Goldmann-correlated and cornea-compensated IOP [adjusted for corneal hysteresis]) in RK patients and myopic controls with POAG. METHODS: Eighty POAG patients (28 RK and 52 myopic controls) were recruited. Central corneal thickness (CCT), prostaglandin analogue (PGA) use, perimetric stage, and history of cataract and glaucoma filtration surgery were assessed through chart review. Participants underwent testing with the ORA (yielding measures of CH, cornea-compensated [IOPcc], Goldmann-correlated IOP [IOPgc], and corneal resistance factor [CRF]), Goldmann applanation, A-scan for axial length (AL), and corneal topography. Slit lamp exam was performed to assess for number of incisions in RK patients. RESULTS: Adjusting for AL and CCT, CH was significantly lower in the RK group with an estimated difference of 0.8585 mmHg (p = 0.0112). Cornea-compensated intraocular pressure was significantly higher in the RK group after controlling for Goldmann applanation, AL, and CCT (2.35 mmHg difference, p < 0.001). Corneal resistance factor and IOPgc were not significantly different. A correlational analysis did not reveal a significant correlation between numbers of RK incisions and CH. CONCLUSIONS: We report significant differences, with lower CH and higher IOPcc, when comparing eyes with glaucoma and either a history of RK or myopia. These findings may aid in establishing normative decreases in CH with RK and POAG and indicate a possible under-estimation of pressure in RK patients.

Polarizable Material from a Conjunctival Biopsy in a Patient with Sarcoidosis.

PURPOSE: Conjunctival biopsies may contain polarizable material in patients with sarcoidosis despite no history of prior trauma or eye surgeries. PROCEDURES: A 39-year-old male with uveitic glaucoma presented with decreased vision and throbbing pain in his right eye. His intraocular pressure was elevated, and his vision was reduced to hand motion. Due to persistently elevated intraocular pressure refractory to medical treatment, the patient underwent a glaucoma drainage device procedure. During the procedure, a yellow, nodular conjunctival growth was noted and biopsied. RESULTS: Histopathological examination revealed multiple nonnecrotizing granulomata, some of which contained polarizable material. CONCLUSIONS: Biopsies of patients with sarcoidosis may contain polarizable material without evidence of foreign body inoculation.

Ocular Hypertension Following Intravitreal Antivascular Endothelial Growth Factor Therapy: Review of the Literature and Possible Role of Nitric Oxide.

PURPOSE: To review the literature regarding ocular hypertension following intravitreal antivascular endothelial growth factor therapy, and to propose a novel mechanism for the development of ocular hypertension as a result of such therapy. METHODS: The PubMed database was used to identify publications by using combinations of the search terms, "glaucoma," "ocular hypertension," "pegaptanib," "bevacizumab," "ranibizumab," "aflibercept," "anti-vascular endothelial growth factor," intraocular pressure," and "intravitreal." The reference lists of these publications were also reviewed for relevant articles. RESULTS: Numerous articles have been published describing ocular hypertension, either immediate-term/short-term or delayed/sustained, following intravitreal antivascular endothelial growth factor therapy. Ocular hypertension has been reported following intravitreal pegaptanib, bevacizumab, and ranibizumab, and aflibercept. On the basis of the fact that vascular endothelial growth factor, normally present as a vascular modulating and reparative growth factor, is known to upregulate endothelial nitric oxide (NO) synthase, and that NO has been shown to decrease intraocular pressure in both normal and glaucomatous human and animal eyes, we propose a novel mechanism for sustained ocular hypertension following intravitreal antivascular endothelial growth factor therapy. We propose that such intravitreal therapy may lead to decreased NO in the anterior segment, which then leads to trabecular meshwork constriction, decreased outflow facility, and increased intraocular pressure. CONCLUSIONS: Sustained ocular hypertension following the intravitreal administration of antivascular endothelial growth factor agents is a potentially serious side effect that has not been adequately explained. Further investigation is necessary to determine the role of NO in the mediation of this adverse effect.

High intraocular pressure following anti-vascular endothelial growth factor therapy: proposed pathophysiology due to altered nitric oxide metabolism.

The nitric oxide (NO) pathway and its physiological significance on relaxing smooth muscle and endothelial cells throughout the body is well outlined and understood. Components of this pathway have been located in the ocular anterior and posterior chambers, and they have been connected with vascular, retinal, and trabecular meshwork normal physiology. Nitric oxide has been shown to increase anterior chamber aqueous outflow via reduction in trabeculocyte size and smooth muscle contractility, and Schlemm's canal vasodilation. Anti-vascular endothelial growth factor (VEGF) therapy has been shown to disrupt the normal nitric oxide signaling pathway, producing systemic arterial hypertension following systemically administered anti-VEGF in oncology by exactly that mechanism. Intravitreal anti-VEGF therapy is now considered a standard of care in several retinal diseases. Sustained elevated intraocular pressure (IOP) has been described as a potential adverse effect of therapy that appears related to the number of injections, and it can be produced by any of the various anti-VEGF compounds. We propose a novel mechanism responsible for the increase in IOPs following prolonged intravitreal anti-VEGF therapy. This mechanism postulates a rise in IOP due to a decrease in aqueous outflow from relatively decreased levels of available nitric oxide in the anterior chamber because of anti-VEGF inhibition of nitric oxide synthase. This article outlines the novel mechanism, which provides a likely explanation for this consequence, along with offering therapeutic targets for future research and treatment.

Trimanual Anterior Vitrectomy: A Novel Technique to Manage Vitreous Loss during Phacoemulsification.

We report 2 cases illustrating the use of a new technique to manage vitreous loss during phacoemulsification, which we have termed 'trimanual' anterior vitrectomy. In each case, after recognizing posterior capsule tear, the remaining nuclear pieces were removed with low-parameter phacoemulsification. The remaining cortical material was then removed using bimanual irrigation and aspiration handpieces while the assistant surgeon inserted the vitrectomy probe through a separate 1-mm limbal incision. The vitrectomy probe was held below the plane of the posterior capsule tear, used to cut the vitreous and to provide a mechanical blockade to potentially descending lens material. While this technique involves the potentially awkward simultaneous use of 3 intraocular instruments, we believe that there are several advantages over standard bimanual anterior vitrectomy.

Bilateral acute iris transillumination following systemic moxifloxacin for respiratory illness: report of two cases and review of the literature.

PURPOSE: To describe two cases of bilateral acute iris transillumination following systemic administration of moxifloxacin and review the literature. METHODS: Review of clinical records, and review of the literature using the PubMed database. RESULTS: A 75 year-old man and 33 year-old woman presented with bilateral conjunctival injection, photophobia, and atonic, distorted pupils. The symptoms began acutely following a respiratory illness, for which both were treated with moxifloxacin. Both patients demonstrated profound iris transillumination, sectoral posterior bowing of the iris, corneal endothelial pigment dusting, and trabecular meshwork hyperpigmentation. One patient had a cotton-wool spot. A literature review identified 59 previous reports in 5 publications, including 17 patients with no antecedent fluoroquinolone use. CONCLUSIONS: Increased awareness of this recently described clinical entity should lead to a decrease in unnecessary diagnostic evaluations. It is currently unclear whether this disease represents an adverse effect of fluoroquinolone use or a sequela of a systemic illness.