Richard Casey

Levofloxacin for chronic prostatitis/chronic pelvic pain syndrome in men: a randomized placebo-controlled multicenter trial.

OBJECTIVES To perform a Canadian multicenter randomized placebo-controlled trial to evaluate the safety and efficacy of 6 weeks of levofloxacin therapy compared with placebo in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Uncontrolled studies have supported the use of antibiotics in CP/CPPS. METHODS Men with a National Institutes of Health (NIH) diagnosis of CP/CPPS (specifically, no infection localized to the prostate) were randomized to levofloxacin (500 mg/day) or placebo for 6 weeks in 11 Canadian centers. Patients were assessed at baseline and at 3, 6, and 12 weeks with the NIH Chronic Prostatitis Symptom Index (NIH-CPSI) and global patient assessments (subjective global assessment and patient assessment questionnaire). RESULTS Eighty men (average age 56.0 years, range 36 to 78; duration of symptoms 6.5 years, range 0.6 to 32) were randomized to receive levofloxacin (n = 45) or placebo (n = 35). All were evaluated in an intent-to-treat analysis. Both groups experienced progressive improvement in symptoms as measured by the NIH-CPSI. However, the difference in response was not statistically or clinically significant at end of treatment (6 weeks) or at the end of the follow-up visits (12 weeks). No patients withdrew because of adverse events. One patient withdrew before the 6-week assessment. Adverse events (all mild) were reported in 20% of the levofloxacin group and 17% of the placebo group. CONCLUSIONS This pilot placebo-controlled study showed that 6 weeks of levofloxacin therapy in men diagnosed with CP/CPPS resulted in symptom improvement that was not significantly different from that with placebo at end of treatment or follow-up. The clinical ramifications of these findings need to be addressed.

Factors Controlling Ocular Angiogenesis

PURPOSE To provide an overview of the cellular and molecular factors involved in ocular angiogenesis. METHODS A literature search and review encompassing a broad range of medical and basic science disciplines was undertaken to survey contemporary insights into the mechanisms of angiogenic stimulation and inhibition. RESULTS Ocular angiogenesis is a complex pathophysiologic process. Factors have been isolated that play key roles in the regulation of angiogenesis. The influence of stimulating growth factors is counterbalanced by a number of antiproliferative agents. The net result of these opposing factors on the vascular endothelial cell determines the outcome of angiogenesis homeostasis. Both endogenous and synthetic molecules can regulate ocular angiogenesis. CONCLUSIONS The isolation and synthesis of molecular regulators of angiogenesis has enhanced our understanding of this process. Clinical trials are underway to determine the efficacy of these agents in controlling pathologic angiogenesis, including that in ocular disease.

Clinical Experience With the Ahmed Glaucoma Valve Implant in Eyes With Prior or Concurrent Penetrating Keratoplasties

PURPOSE To evaluate the Ahmed Glaucoma Valve implant, an aqueous shunting device with a unidirectional valve mechanism, in eyes with concurrent or prior penetrating keratoplasties. METHODS Thirty-one eyes of 31 consecutive patients had placement of an Ahmed Glaucoma Valve implant. Median patient age was 65.1 years (range, 17.2 to 103.4 years). The main outcome measure was time after surgery without failure. Success was defined as no additional glaucoma surgeries or devastating visual complications, no new corneal graft failure, an intraocular pressure greater than or equal to 5 mm Hg on the last two follow-up examinations, and reduction in intraocular pressure. For eyes with preoperative intraocular pressure greater than 22 mm Hg, an average intraocular pressure of less than 22 mm Hg on the last two follow-up examinations was required. For eyes with preoperative intraocular pressure of less than 22 mm Hg, an intraocular pressure lowered by at least 20% from preoperative values was required. RESULTS Cumulative probabilities of success at 12 and 20 months (mean +/- SD) were 75.4% +/- 8.2% and 51.5% +/- 11.4%, respectively. Eleven of 31 eyes were failures. The risk of failure in eyes with prior infectious keratitis or keratouveitis was estimated to be 5.8 times greater than that associated with eyes that underwent penetrating keratoplasties for other reasons (P = .009). CONCLUSIONS Twelve- and 20-month success rates of the implant in eyes with prior or concurrent penetrating keratoplasties were comparable to those of other drainage devices. Eyes with prior infectious keratitis or keratouveitis were at increased risk of failure.

A multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of terazosin in the treatment of benign prostatic hyperplasia.

OBJECTIVES This study was designed to evaluate the safety and efficacy of the selective alpha 1-adrenoceptor blocker terazosin in the treatment of benign prostatic hyperplasia (BPH). METHODS Two hundred twenty-four patients aged 50 to 80 years, who had a diagnosis of BPH based on medical history, physical examination, and digital palpation, were recruited from 11 different sites between January 1992 and January 1994. The study consisted of a screening phase, a placebo phase, a double-blind dose-titration phase, and a double-blind maintenance phase. RESULTS Of the patients recruited, 164 entered the double-blind phase and of these 134 were evaluable. Only 11 patients withdrew because of an adverse event, 7 in the terazosin and 4 in the placebo group. Compared to placebo, terazosin significantly increased peak and mean urine flow rates without significantly affecting voided volume or postvoid residual volume. It significantly improved both the obstructive and irritative symptoms associated with BPH. Fifty-one patients from the terazosin group reported a total of 120 adverse events compared with 83 reported by 42 patients in the placebo group. The majority of these events were mild to moderate. Seventeen terazosin-treated patients reported hypotension-related adverse events and 4 withdrew from the study. However, concurrent treatment with antihypertensive agents did not affect the blood pressure response of the terazosin group. CONCLUSIONS Overall, this study showed terazosin to be safe and effective in relieving the signs and symptoms of BPH and should be considered as a treatment alternative.

Fluorescein Punctate Staining Traced to Superficial Corneal Epithelial Cells by Impression Cytology and Confocal Microscopy

PURPOSE The basis of fluorescein-associated superficial punctate staining in dry eyes is controversial. Prior explanations include fluorescein pooling in surface erosive defects, intercellular trapping of fluorescein, and intracellular staining in dead cells. In this study, the hypothesis that punctate erosions are individual cells with enhanced fluorescence was tested. METHODS Ten impression cytology membrane materials were compared, to optimize cellular yield in buccal mucosa and cornea. Clinicocytologic correlation of punctate fluorescent spots was performed in four dry eye patients. Individual punctate spots were localized by fiducial marks in photographs, before and after removal with impression membranes, and were traced in fluorescence microscopy and cytologic staining. Two-way contingency table analysis was used to determine the correlation of punctate spots with cells removed by the membrane. Clinicopathologic correlation of punctate spots was performed in 10 corneas removed in dry eye patients by transplantation for concurrent diseases. Punctate fluorescence was tracked in specimens by fiducial marks and epifluorescence. The distribution of fluorescent spots in specific cell layers of the cornea was determined by confocal microscopy. RESULTS Cellular yield was greatest with impressions from polytetrafluoroethylene (PTFE [Teflon]; BioPore; Millipore, Billerica, MA) membrane compared with its closest rival (P = 0.019). Punctate fluorescent spots, most of which disappeared after impression cytology (71%), correlated with cells on the membranes (P = 0.009). The punctate spots were more frequent in the superficial cell layers of the cornea (80%) compared with the deepest two layers (0%) (P < 0.00049). CONCLUSIONS Punctate epithelial erosions correspond to enhanced fluorescence in epithelial cells predominantly in superficial layers of the cornea and would be more aptly named fluorescent epithelial cells (FLECs).

Corneoscleral laceration caused by air-bag trauma

PURPOSE To report a case of a corneoscleral laceration sustained as a direct result of inflation of a driver-side air bag. METHODS A patient who sustained a severe ocular injury in a low-speed motor vehicle accident underwent clinical and radiologic examination and subsequent treatment. RESULTS The left eye underwent primary repair of a complex corneoscleral laceration. Two weeks postoperatively, visual acuity in the left eye remained at bare hand motion. CONCLUSION Although air-bag-related eye trauma may be relatively infrequent, the severity of the injuries incurred warrant research efforts to explore new air-bag designs that minimize the risk of ocular injury.

Graft Failure After Penetrating Keratoplasty in Eyes With Ahmed Valves

PURPOSE To determine incidence and risk factors for graft failure following penetrating keratoplasty (PK) in eyes with Ahmed valves (AV). DESIGN Retrospective, observational cohort study. METHODS Patients who underwent PK after AV implantation (both performed at our institution through 2004) were studied. Intervals to graft failure (defined as either dysfunction [stromal thickening with retention of clarity] or decompensation [central microcystic edema or loss of clarity]) were analyzed using Kaplan-Meier technique. Risk factors for graft failure were analyzed using Cox proportional hazard models. RESULTS Included were 77 eyes (77 patients; first procedure 1993). Following PK, 40 eyes (52%) required increased numbers of glaucoma medications; 10 eyes (13%) required additional glaucoma drainage device(s). Graft failure at 1, 2, and 3 years was 42.4% (95% confidence interval: 32.0%-54.6%), 57.1% (45.6%-69.1%), and 59.1% (47.5%-71.2%), respectively. Prior PK (HR 2.38, P = .006) and stromal vessels (HR 2.90, P = .0005) were associated with increased risk of graft failure. Use of glaucoma medications (HR 0.27, P = .009) and evidence of lower intraocular pressures (IOP) during follow-up (excluding hypotony; HR 0.92, P = .010) were associated with reduced risk of graft failure. Endothelial rejection episodes were observed in 13 eyes (17%); however, rejection was not a risk factor for graft failure (P = .98). CONCLUSIONS Long-term survival of corneal grafts is poor in eyes with AV. The majority of graft failures are associated with progressive loss of endothelial function, without observed immunologic rejection. Despite the presence of an AV, escalation in glaucoma therapy often follows PK; graft failure may be related to poor IOP control.

A double‐blind randomized dose‐response study comparing daily doses of 5, 10 and 15 mg controlled‐release oxybutynin: balancing efficacy with severity of dry mouth

To assess the efficacy, incidence of dry mouth and overall satisfaction with initial doses of 5, 10 and 15 mg of a new, once‐daily, controlled‐release (CR) form of oxybutynin for treating urge urinary incontinence (UUI).

Efficacy and safety of ketotifen fumarate 0.025% in the conjunctival antigen challenge model of ocular allergic conjunctivitis

PURPOSE To determine the duration of action of ketotifen 0.025% eye drops vs placebo taken as single or multiple doses in an allergen challenge model. DESIGN Two randomized, multicenter, double-masked, contralateral placebo-controlled studies, one a single-dose and one a multiple-dose study. METHODS Two conjunctival provocation tests (CPTs) were initially conducted to confirm reproducibility of subject responses in both studies. Subjects in study 1 (n = 87) received single doses of ketotifen in one eye and placebo in the other 15 minutes, 6 hours, and 8 hours before CPT. Subjects in study 2 (n = 85) received ketotifen or placebo once 8 hours before CPT. Single-dose efficacy results were used to further qualify a subject as a responder. Responders were re-randomized to a 4-week twice daily dosing regimen with a CPT 8 hours after the final dose. In both studies, ocular symptoms were assessed at three time points 3 to 15 minutes after challenge. There were no significant differences in adverse events between groups. RESULTS For both studies, ocular itching and vascular injection were significantly reduced (P <.003) at all time points after instillation of ketotifen, with a maximum reduction at 7 minutes postchallenge. In study 2, chemosis, tearing, and lid swelling were also assessed and were significantly reduced (P <.008) after instillation of ketotifen. CONCLUSIONS Ketotifen 0.025% eye drops were safe and statistically effective in preventing ocular itching, injection, and other signs and symptoms of allergic conjunctivitis at 15 minutes, 6 hours, and 8 hours after a single dose and at 8 hours after the final dose of a 4-week twice daily regimen.

Prevalence and causes of low vision and blindness in the Extreme North Province of Cameroon, West Africa

A survey to determine the prevalence and causes of blindness and visual impairment in the Extreme North Province of Cameroon was conducted in the Spring of 1992. A total of 10,647 people age 6 years and older was selected from a multi-stage, clustered sample stratified by ecological zone. The subjects were examined by ophthalmologist-led teams for visual acuity and ocular diseases. Approximately 1.2% of the sample was bilaterally blind by the World Health Organization classification (Category 3) of vision less than the ability to count fingers at 3 meters. Similarly to results found in other developing countries, senile cataract was the most common diagnosis encountered and the most frequent principal cause of low vision and blindness.