Genome Sequencing and Apoptotic Markers to Assess Treatment Response of Lacrimal Gland Adenoid Cystic Carcinoma to Intra-Arterial Cytoreductive Chemotherapy.

Adenoid cystic carcinoma of the lacrimal gland is an aggressive, malignant epithelial neoplasm. We report the case of a 30-year-old male with lacrimal gland adenoid cystic carcinoma treated with neoadjuvant intra-arterial chemotherapy through the internal carotid artery, followed by orbital exenteration and chemoradiation. Treatment response was evaluated using a novel combination of pre- and posttreatment genome sequencing coupled with immunohistochemical evaluation, which showed diffuse tumor apoptosis. A posttreatment decrease in variant allele frequency of the NOTCH1 mutation, and robust tumor cytoreduction on imaging, supports exploration of NOTCH1 analysis as a potential marker of cisplatin sensitivity. The use of genome sequencing and immunohistochemical evaluation could provide a more targeted therapeutic assessment of neoadjuvant intra-arterial chemotherapy in the management of lacrimal gland adenoid cystic carcinoma.

Histologic Artifacts of Autolytic Müller Cell Foot Process Swelling in Postmortem Examination of Infant Eyes: Potential Pitfall in the Evaluation of Traumatic Retinal Hemorrhages.

IMPORTANCE: Retinal hemorrhages are an important sequela of fatal head trauma. The accurate pathologic diagnosis of retinal hemorrhages has critical implications for determination of the manner of death. OBSERVATIONS: We describe an autolytic postmortem histologic artifact of eosinophilic Müller cell foot process swelling that mimics a nerve fiber layer hemorrhage. From April 24, 2012, through November 11, 2014, we conducted postmortem examination of the eyes of 23 infants and children who were referred to our institution for possible nonaccidental head trauma. A focal artifact of Müller cell foot process swelling was identified in most patients (16 of 23) up to 4 years of age. Three infants, all of whom were younger than 3 months, demonstrated diffusely swollen Müller cell foot processes with intensely eosinophilic cytoplasm that mimicked erythrocytes of nerve fiber layer hemorrhages. The difference in the mean age between patients with diffuse eosinophilic artifacts (1.7 months) and patients with only a multifocal, focal, or absent artifact (13.3 months) was 11.6 months (95% CI, 6.5-16.7 months). Glycophorin C immunohistochemical analysis was useful to differentiate this artifact from nerve fiber layer hemorrhage. CONCLUSIONS AND RELEVANCE: Our case review demonstrates an artifact of eosinophilic Müller cell foot processes swelling in postmortem examination of young infant eyes, a potential pitfall in the diagnosis of retinal hemorrhages. Our findings have important implications for the diagnosis of retinal hemorrhages in potential cases of nonaccidental head injury.

Histopathologic correlation of Aspergillus endophthalmitis following uncomplicated cataract surgery.

A clinicopathologic correlation between two patients with acute-onset Aspergillus endophthalmitis undergoing enucleation is reported. These two patients presented with pain, redness, and decreased vision following uncomplicated cataract surgery. In both patients, vitreous aspiration and intravitreal injections were the initial treatment followed later by pars plana vitrectomy for clinical worsening. Despite repeated surgical and medical interventions, the clinical course of both patients was prolonged, unsuccessful, and resulted in enucleation for a blind painful eye. Histologic examination of the enucleated specimens showed that, in spite of prolonged local and systemic therapy, there was persistent diffuse infiltration of the anterior chamber and ciliary body by a filamentous mold.

Long-term comparison of primary trabeculectomy with 5-fluorouracil versus mitomycin C in West Africa.

PURPOSE: To compare the long-term efficacy and safety of intraoperative 5-fluorouracil (5-FU) versus mitomycin-C (MMC) used adjunctively with primary trabeculectomy in a Black West African population. DESIGN: Retrospective comparative study supplemented with cross-sectional follow-up data. METHODS: Review of 68 eyes of 68 Black West African subjects that underwent primary trabeculectomy with the use of intraoperative 5-FU or MMC between January 1, 1988 and January 1, 2002 and had at least 3 years postoperative follow-up. Postoperative outcome measures included intraocular pressure (IOP) control, number of glaucoma medications, visual acuity, and complications. RESULTS: Thirty-eight of sixty-eight eyes received 5-FU and 30 received MMC. Mean postoperative follow-up was 7.5 and 6.5 years in the 5-FU and MMC groups, respectively (P=0.17). A higher proportion of eyes in the MMC group achieved "qualified" (with or without medical therapy) success with varying IOP targets relative to the 5-FU group, but the differences were not statistically significant. "Complete" (without medical therapy) postoperative success was greater in the MMC group with a significantly higher proportion achieving an IOP <21 mm Hg (P=0.02). MMC use was also associated with a lower likelihood of receiving IOP-lowering medications postoperatively (P=0.01). Baseline demographic characteristics, preoperative and postoperative IOP, visual acuity, and complications did not differ significantly between the 2 groups. CONCLUSIONS: Intraoperative MMC use is associated with a lower likelihood of requiring postoperative medications and a greater likelihood of achieving IOP lowering without medications relative to the use of 5-FU in a Black West African population.

ThinPrep vitreous-based diagnosis of choroidal malignant melanoma.

PURPOSE: To report an alternative method for the diagnosis of atypical choroidal malignant melanoma-ThinPrep sampling of the vitreous cavity through 25-gauge vitrectomy. METHOD: Case report. RESULTS: A 79-year-old gentleman presented with a progressive decline in visual acuity in his left eye. A clinical diagnosis of large choroidal malignant melanoma was made. Given the history of trauma and the possibility of enucleation, the patient wished to have histopathological confirmation. The patient underwent 25-gauge vitrectomy. However, he developed a choroidal hemorrhage during the procedure and the surgeon elected not to perform transretinal biopsy. Instead a sample of the vitreous was evaluated by ThinPrep analysis, and a diagnosis of choroidal malignant melanoma was made. CONCLUSIONS: Cytological evaluation of vitreous substance with ThinPrep may provide an alterative method for a diagnosis in select cases in which FNA is not possible or desirable. This technique is straightforward and minimizes the risk of retinal detachment or hemorrhage.

Comparison of one-day versus one-hour application of topical gatifloxacin in eliminating conjunctival bacterial flora.

PURPOSE: To compare efficacies of 1-day, 1-hour, and combined 1-day/1-hour preoperative topical gatifloxacin in eliminating conjunctival bacterial flora. DESIGN: Prospective, comparative case series. PARTICIPANTS: Sixty patients (120 eyes) scheduled to undergo anterior segment intraocular surgery at Stanford University Medical Center. METHODS: Cultures were collected from the palpebral conjunctival sac at baseline and after 1 day (4 doses), 1 hour (3 doses), and 1 day/1 hour (7 doses) of gatifloxacin use. MAIN OUTCOME MEASURES: Incidence of positive bacterial samples collected pre- and post-antibiotic treatment and number of colony forming units (CFUs). RESULTS: SeptiChek (Becton Dickinson, Franklin Lakes, NJ) positive cultures significantly decreased from 67% growth at baseline to 28% (P<0.0001) after 1 day and from 60% at baseline to 37% (P = 0.018) after 1 hour of gatifloxacin use. Reductions of 44% growth at baseline to 12% (P = 0.0001) after 1 day and 32% at baseline to 13% (P = 0.029) after 1 hour of gatifloxacin use were observed on blood agar. Surgical eyes that received both 1-day and 1-hour preoperative gatifloxacin had reductions from 67% growth at baseline to 18% posttreatment (P<0.0001) and 45% at baseline to 7% posttreatment (P<0.0001) on SeptiChek and blood agar media, respectively. In addition to a lower frequency of positive cultures, a significantly lower CFU count was found after 1-day (P = 0.004) and 1-hour (P = 0.049) gatifloxacin use compared with pretreatment levels. Combined 1-day/1-hour doses of gatifloxacin were associated with a greater reduction in CFUs (P = 0.001) when compared with 1-hour treatment alone. CONCLUSIONS: Both 1-hour and 1-day topical gatifloxacin use are effective in reducing the frequency of conjunctival bacterial growth and the overall bacterial load as measured by CFUs, relative to baseline. Although a 1-hour pretreatment is associated with a reduction in bacterial growth, the combination of 1-day and 1-hour preoperative gatifloxacin dosing results in an even lower overall bacterial load, suggesting that the latter might be the preferred preoperative regimen for eyes undergoing anterior segment surgery.

Orbital giant cell angiofibroma recurring as a solitary fibrous tumor.

Giant cell angiofibroma has recently been hypothesized to be a clinicopathologic variant of solitary fibrous tumor. The authors report a case of an orbital giant cell angiofibroma that recurred as a solitary fibrous tumor 4 years later. The report strongly supports the hypothesis that giant cell angiofibroma and solitary fibrous tumor are related.

Prospective comparison of topical moxifloxacin in eliminating conjunctival bacterial flora following a one-day or one-hour application.

PURPOSE: The aim of this study was to compare the efficacy of a 1-hour(h) versus 1-day application of topical moxifloxacin in eliminating conjunctival bacterial flora. METHODS: In this prospective, nonrandomized, controlled trial, the surgical eyes of 60 patients scheduled for intraocular surgery received topical moxifloxacin four times a day, starting 1 day prior to surgery and three additional applications at 5-minute intervals 1 h before surgery. The nonsurgical eye of each patient only received three applications of the same antibiotic at 5-minute intervals 1 h before surgery. Conjunctival cultures were obtained at baseline and after antibiotic application. RESULTS: Prior to antibiotic application, 80% of surgical eyes and 70% of nonsurgical eyes had positive cultures. Following the 1-day application, significantly fewer eyes (40%) had positive cultures (P < 0.0001), with a further reduction to 32% with three additional doses 1 h prior to surgery. In the nonsurgical eye, the decrease in the percentage of positive cultures, from 55% to 53% following the three applications 1 h prior to surgery, was not significant (P > 0.9999). The 1-day application was associated with significantly fewer positive cultures, compared to the 1-h group (P = 0.0267). CONCLUSIONS: The one-day application of moxifloxacin resulted in significantly fewer positive conjunctival cultures, compared with a 1-h application.

Prospective randomized comparison of 2 different methods of 5% povidone-iodine applications for anterior segment intraocular surgery.

OBJECTIVE: To determine the efficacy of reducing conjunctival bacteria flora with 2 different regimens of 5% povidone-iodine application: 2 drops on the conjunctiva cul-de-sac vs a 10-mL conjunctival irrigation of the fornices. METHODS: In this prospective controlled trial, 200 eyes undergoing anterior segment intraocular surgery were randomized to control and study groups. All patients from both groups received topical ofloxacin and a povidone-iodine scrub of the periorbital area before the surgical procedure. The eyes in the control group received 2 drops of povidone-iodine on the conjunctiva preoperatively, whereas eyes in the study group had irrigation of the fornices with 10 mL of povidone-iodine. Conjunctival cultures were obtained at 4 separate time points before and after surgery. RESULTS: Twenty (26%) of 78 eyes in the study group had positive conjunctival cultures immediately prior to surgery compared with 40 (43%) of 94 eyes in the control group (P = .02). At the conclusion of the surgery, 14 (18%) of 78 eyes and 30 (32%) of 94 eyes had positive cultures in the study and control groups, respectively (P = .05). CONCLUSION: Irrigation of the fornices with 5% povidone-iodine was associated with significantly fewer positive conjunctival cultures at the time of surgery compared with the application of 2 drops on the conjunctiva.

Three-day application of topical ofloxacin reduces the contamination rate of microsurgical knives in cataract surgery: a prospective randomized study.

PURPOSE: To determine the rate of contamination of microsurgical knives during cataract surgery and the benefit of a 3-day versus a 1-hour preoperative application of topical ofloxacin in reducing the contamination rate. DESIGN: Prospective, randomized controlled trial. PARTICIPANTS: Seventy-eight eyes of 75 patients were randomly assigned to control (39 eyes) or study groups (39 eyes). METHODS: All patients from both groups received 0.3% topical ofloxacin 1 hour before surgery, 5% povidone-iodine (PVI) scrub of the periorbital area, and 2 drops of PVI onto the ocular surface preoperatively. The patients in the study group also received ofloxacin 4 times a day for 3 days before surgery. MAIN OUTCOME MEASURES: Microsurgical knives were placed in blood culture broth media immediately after the incision had been made. The number of positive cultures and types of bacteria isolated were determined. RESULTS: Ten of 39 knives (26%) in the control group were found to be positive for bacterial growth compared with only 2 of 39 (5%) in the study group (P = 0.028). CONCLUSIONS: The initial paracentesis incision frequently results in contamination of the microsurgical knife and may serve as a mechanism for introducing bacteria from the ocular surface into the anterior chamber. The application of topical ofloxacin for 3 days before surgery significantly reduces the contamination rate of the microsurgical knives, compared with a preoperative application of ofloxacin given 1 hour before surgery.

The challenge of determining aqueous contamination rate in anterior segment intraocular surgery.

PURPOSE: To determine aqueous contamination rate in anterior segment intraocular surgery using two different techniques of obtaining aqueous fluid and to assess whether a 3-day application of topical 0.3% ofloxacin reduces this contamination rate compared with a 1-hour application. DESIGN: Randomized clinical trial. METHODS: One hundred and thirty-three eyes of 130 patients undergoing anterior segment intraocular surgery were randomized to either control (64 eyes received topical ofloxacin 1 hour before surgery) or study groups (69 eyes received topical ofloxacin four times a day for 3 days before surgery in addition to 1 hour preoperatively). Eyes in both groups received a periorbital iodine scrub and two drops of topical 5% iodine. Aqueous fluid was obtained at the beginning and conclusion of surgery using a cannula passed through a paracentesis or a needle passed through clear cornea. The aqueous, cannula, and needles were inoculated in blood culture media broth and bacterial growth was identified. RESULTS: Overall, eight of 89 aqueous samples (9%) obtained using a cannula at the beginning of surgery were culture-positive. Similarly, six of 41 aqueous samples (15%) obtained through a needle through clear cornea at the beginning of surgery showed contamination. At the conclusion of surgery, nine of 112 samples (8%) showed positive cultures. There was no difference in the aqueous contamination rates between the control and study groups. CONCLUSIONS: Despite the use of a needle to obtain aqueous fluid at the beginning of surgery before creating a paracentesis, the aqueous contamination rate remained higher than that found at the conclusion of surgery. A 3-day application of topical ofloxacin before surgery did not reduce the anterior chamber aqueous contamination rate relative to a 1-hour application.

Antibiotic resistance patterns of ocular bacterial flora: a prospective study of patients undergoing anterior segment surgery.

PURPOSE: To determine the antibiotic susceptibility patterns of conjunctival bacterial flora isolated preoperatively from patients undergoing anterior segment surgery. DESIGN: Prospective observational study. PARTICIPANTS: One hundred fifty-six eyes from 139 patients scheduled for anterior segment surgery were enrolled over a 6-month period from August 2001 to February 2002. METHODS: Conjunctival cultures were obtained on the day of surgery before povidone-iodine or antibiotic application. MAIN OUTCOME MEASURES: Bacterial isolates were identified and tested for antibiotic susceptibility using the Kirby-Bauer disc-diffusion technique. RESULTS: Among the 156 eyes studied, 36 were from patients who had undergone either bilateral surgery or more than one surgery in the same eye. Only the first eyes of the 120 patients that underwent initial ocular surgery were included in our analysis. Of these 120 eyes, 21 (18%) showed no bacterial growth. Of the 143 bacterial strains isolated from the remaining 99 eyes, 112 (78%) were coagulase-negative staphylococci (CNS). Among the CNS, greater than 90% were susceptible to cefotaxime, levofloxacin, imipenem, meropenem, vancomycin, and each of the aminoglycosides except neomycin. Between 70% and 90% of the CNS were susceptible to cefazolin, neomycin, ciprofloxacin, ofloxacin, norfloxacin, and chloramphenicol. Less than 70% of the isolated CNS were sensitive to the penicillin analogues, ceftazidime, erythromycin, and tetracycline. CONCLUSIONS: Preoperative conjunctival isolates of CNS seem to be most sensitive to vancomycin, the aminoglycosides (except neomycin), and levofloxacin.

Risk factors for antibiotic-resistant conjunctival bacterial flora in patients undergoing intraocular surgery.

BACKGROUND: The purpose of this study was to determine if patients with certain risk factors are more likely to harbor conjunctival bacterial flora resistant to multiple antibiotics. METHODS: In this prospective study, detailed medical history and slit-lamp examination were performed on all patients prior to intraocular surgery. Patients with local risk factors were defined as those with chronic blepharitis, conjunctivitis or discharge. Those with systemic risk factors were patients with diabetes, autoimmune, immunodeficient or skin disorders, asthma and those taking immunosuppressant medications. Conjunctival cultures were obtained prior to preoperative antibiotics and povidone-iodine. Bacteria isolated were identified and antibiotic susceptibility was determined. Bacteria resistant to five or more antibiotics were defined as multi-resistant (MR). RESULTS: Among the 207 patients enrolled in the study, 73 patients had local risk factors. Of these patients, 32 patients (44%) carried MR organisms, compared to 32 of the 134 patients (24%) without local risk factors (P=0.0049). Thirty-two of 71 patients (45%) with systemic risk factors harbored MR organisms, compared to 32 of 136 patients (24%) without systemic risk factors (P=0.0025). Seventeen of 93 patients (18%) who had neither local nor systemic risk factors had MR organisms on their conjunctiva. In contrast, 17 of the 30 patients (57%) with both local and systemic risk factors (57%) carried MR bacteria (P=0.0001). CONCLUSION: Patients with local and/or systemic risk factors are more likely to harbor MR organisms. This may be one mechanism for the reported increased risk of postoperative endophthalmitis in this group of patients.

Prospective randomized comparison of 3-day versus 1-hour preoperative ofloxacin prophylaxis for cataract surgery.

PURPOSE: To determine the efficacy of reducing conjunctival bacterial flora with topical ofloxacin when given for 3 days compared with 1 hour before surgery. DESIGN: Prospective, randomized, controlled trial. PARTICIPANTS: Ninety-two eyes from 89 patients were randomized to a control group (48 eyes) or study group (44 eyes). METHODS: All patients from both groups received topical ofloxacin 0.3% 1 hour before surgery and a 5% povidone iodine scrub of the periorbital area before surgery. The patients in the study group received additional ofloxacin four times daily for 3 days before surgery. MAIN OUTCOME MEASURES: Conjunctival cultures were obtained at five separate time points and were inoculated in solid and liquid culture media. The presence of bacteria was determined, quantified, and identified. RESULTS: Forty-two percent of eyes in the control group had positive conjunctival culture immediately before surgery, compared with 19% of eyes in the study group (P < 0.05). Immediately after surgery, 34% and 14% of eyes had positive cultures in the control and study groups, respectively (P < 0.05). Quantitatively, fewer bacteria were isolated from eyes in the study group compared with those in the control group for culture samples that were obtained both before povidone iodine scrub and at the conclusion of surgery (P

Glaucoma in West Africa: a neglected problem.

Glaucoma in sub-Saharan Africa is a devastating disease which has not been fully addressed by the global ophthalmology community. The key issue is the lack of a satisfactory treatment.