Colin A. McCannel

Meta-analysis of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents: causative organisms and possible prevention strategies.

Purpose: To report the rates of endophthalmitis and the spectrum of causative organisms after intravitreal injection of anti-vascular endothelial growth factor agents and possible prevention strategies. Methods: Meta-analysis of the U.S. literature from 2005 to 2009 reporting endophthalmitis bacterial isolates after intravitreal injection of anti-vascular endothelial growth factor agents and comparison with reports of endophthalmitis bacterial isolates after intraocular surgery in the United States. Results: Endophthalmitis after intravitreal injection occurred in 52 of 105,536 injections (0.049%) (95% confidence interval [CI], 0.038-0.065%). Among 50 cases of endophthalmitis with bacterial culture isolates, 24 (48.0% [95% CI, 34.8-61.5%]) were culture negative and 26 (52% [95% CI, 38.5-65.2%]) were culture positive. Among the 26 culture-positive isolates, causative organisms were coagulase-negative Staphylococcus in 17 cases (65.4% [95% CI, 46.0-80.6%]), Streptococcus species in 8 cases (30.8% [95% CI, 16.5-50.2%]), and Bacillus cereus in 1 case (3.8% [95% CI, 0.9-19.0%]). Streptococcus species were significantly more frequent after intravitreal injection than after intraocular surgery in the Endophthalmitis Vitrectomy Study (29 of 226 isolates, 9.0% [95% CI, 6.3-12.6%], P = 0.005), a report on clear corneal cataract surgery endophthalmitis (6 of 73 isolates, 8.2% [95% CI, 3.9-16.8%], P = 0.022), and a report on postvitrectomy endophthalmitis with no cases of Streptococcus species. Conclusion: Streptococcal isolates are approximately three times more frequent after intravitreal anti-vascular endothelial growth factor injection than after intraocular surgery. Strategies to consider minimizing oropharyngeal droplet transmission may include avoiding talking, coughing, and sneezing or wearing surgical masks.

Six-month stability of bevacizumab (Avastin) binding to vascular endothelial growth factor after withdrawal into a syringe and refrigeration or freezing.

Purpose: To determine the change in anti–vascular endothelial growth factor (VEGF) activity of bevacizumab (Avastin, Genentech, Inc., San Francisco, CA) after refrigeration or freezing. Methods: Samples of bevacizumab were drawn up from new vials into plastic tuberculin syringes and refrigerated at 4°C for 1 week, 3 weeks, 1 month, 3 months, and 6 months. The vials and syringes were stored at 4°C, and the syringes were capped with a needle. One syringe was frozen at −10°C. The bevacizumab concentration was measured, via its binding to VEGF-165. Results: The percentage of degradation of bevacizumab in the previously pierced vials stored at 4°C compared with that in the unpierced vial was 9.6% at 3 months and 12.7% at 6 months. The bevacizumab drawn into the syringe and stored at 4°C was degraded by 1.6% at 1 week, 0% at 3 weeks, 8.8% at 3 months, and 15.9% at 6 months. The bevacizumab frozen in a syringe at −10°C was degraded by 12.0% at 6 months. Conclusion: The anti-VEGF activity of bevacizumab may degrade minimally over time, with storage.

Infectious endophthalmitis after intravitreal injection of antiangiogenic agents.

Purpose: To evaluate the rate of infectious endophthalmitis associated with intravitreal injection of bevacizumab, ranibizumab, and pegaptanib sodium. Methods: A retrospective review of patients who received intravitreal injections of bevacizumab, ranibizumab, and pegaptanib sodium was undertaken. Cases of clinical diagnoses of endophthalmitis or suspected endophthalmitis resulting from intravitreal injection were identified and reviewed. From these data, the risk per injection was estimated. Results: Three patients developed endophthalmitis after the intravitreal injection. The risk per injection was 0.00077 (0.077%). The rate of endophthalmitis was 1 per 1,291 injections. Conclusion: A similar risk of endophthalmitis per injection compared with some trials was obtained in this study. Although no definite risk factors could be identified, intravitreal injections performed by nonretina specialist physicians may be a risk factor for the development of endophthalmitis.

Population-based Incidence of Macular Holes

PURPOSE To determine the incidence of full-thickness macular holes in Olmsted County, Minnesota. DESIGN Population-based retrospective chart review (cross-sectional study). PARTICIPANTS Ninety-four eyes of 85 patients who were residents of Olmsted County, Minnesota. METHODS A population-based retrospective chart review was performed for all diagnoses of macular hole between 1992 and 2002 among residents of Olmsted County, Minnesota. Yearly incidence rates for each given age and sex group were determined by dividing the number of cases within that group by the estimated total Olmsted County resident population of the group for that given year. MAIN OUTCOME MEASURES Documented clinical diagnosis of a macular hole. RESULTS Idiopathic macular holes occur at an age- and sex-adjusted incidence in 7.8 persons and 8.69 eyes per 100,000 population per year in Olmsted County, Minnesota. The female-to-male ratio was determined to be 3.3 to 1, and bilateral idiopathic macular holes occurred in 11.7% of patients and accounted for 20.9% of the affected eyes. CONCLUSIONS This study uniquely determined the incidence of macular holes in a predominantly Caucasian population.

Acute macular neuroretinopathy: long-term insights revealed by multimodal imaging.

Purpose: To report the structural and functional changes in acute macular neuroretinopathy (AMN) and their long-term evolution. Multimodal retinal imaging was acquired, including Fourier domain optical coherence tomography (OCT), infrared (IR) reflectance, and near IR autofluorescence (NIA). Methods: In this retrospective observational case series, detailed clinical history and multimodal imaging are reported in eight patients with AMN. Manual segmentation of the Fourier domain OCT volume scans was done in one patient with the largest AMN lesion to yield retinal sublayer topographic maps. Results: Two patients were seen within the first 1 to 2 days of symptoms, and both showed outer nuclear and outer plexiform layer hyperreflectivity. Both patients developed enlargement of the lesion over the first week on IR reflectance imaging with a corresponding lateral extension of the outer retinal disruption on Fourier domain OCT. Thinning of the outer nuclear layer persisted in all patients with lesions >100 &mgr;m width, and in one patient this thinning worsened over the course of follow-up, as noted on the sublayer maps. This structural abnormality correlated with long-term functional deficits, persisting up to 14 months after the initial episode. Infrared reflectance highlights the lesion best, and abnormalities on near IR autofluorescence may be present. Conclusion: Acute macular neuroretinopathy acutely affects the outer nuclear and plexiform layers manifesting as OCT hyperreflectivity. The hallmark long-term changes are outer nuclear thinning on Fourier domain OCT and a fading dark lesion on IR reflectance imaging. These changes correspond to focal disruption of the outer segment/retinal pigment epithelium junction on OCT, and not the inner segment/outer segment junction, as previously reported. Optical coherence tomography and near IR autofluorescence abnormalities suggest previously unrecognized melanin and retinal pigment epithelium derangements in this condition.

Acetazolamide but not timolol lowers aqueous humor flow in sleeping humans

The effect of timolol, acetazolamide, and the combination of the two drugs on the rate of aqueous formation in 18 healthy human subjects was measured during the day and at night in a placebo-controlled, double-masked, randomized study. In the absence of any drugs, aqueous flow during the day was 2.61 ±0.82 (mean ± SD) μl/min and at night, 1.08±0.59, a 59 lower flow rate when compared with the daytime value (P<0.0001). When compared with these aforementioned control values, timolol alone reduced the rate of aqueous flow by 39% (P<0.0001) in awake subjects but had no statistically significant effect on the flow rate in sleeping subjects (P=0.33). Acetazolamide alone reduced aqueous flow during the day by 21% compared with the control flow rate (P=0.02) and at night by 24% below the nocturnal flow rate in the sleeping eye (P=0.04). The combination of the two drugs reduced flow during the day by an additional 13% (P=0.024) compared with the flow rate achieved by timolol alone, and by an additional 32% (P<0.0001) compared with the flow rate reduction attained by acetazolamide alone. There was no statistically significant difference in the nocturnal flow rates achieved by acetazolamide alone or in combination with timolol (P=0.37). These data confirm previous studies demonstrating the effect of timolol, acetazolamide, and sleep on the rate of aqueous humor formation. Unlike a previous study, it was found that acetazolamide lowers the aqueous flow below the already low nocturnal flow rate that occurs spontaneously in the sleeping eye. It appears that the mechanisms which mediate the effects of sleep, timolol, and acetazolamide on aqueous formation are all different and that in the case of timolol a state of wakefulness is required for a measurable effect to occur.

Intravitreal injection technique and monitoring: updated guidelines of an expert panel.

Purpose: To review evidence and provide updated guidelines on intravitreal (IVT) injection technique and monitoring. Methods: A review of the published literature on IVT injection from 2004 to 2014 formed the basis for round table deliberations by an expert panel of ophthalmologists. Results: The dramatic increase in the number of IVT injections has been accompanied by a comparable increase in evidence surrounding IVT practice patterns and techniques. The expert panel identified a number of areas that have evolved since publication of the original IVT injection guidelines in 2004, the most notable of which were a lack of evidence to support the routine use of pre-, peri-, and postinjection antibiotics to reduce the risk of endophthalmitis, and the role of aerosolized droplets containing oral contaminants from the patient and/or providers as a potential source of infection. The panel emphasized the continued importance of applying povidone–iodine to and avoiding eyelid contact with the intended injection site and needle. Conclusion: Updated guidelines on IVT injection technique and monitoring are proposed based on a review of published literature and expert panel deliberations.

Special Requirements for Electronic Health Record Systems in Ophthalmology

UNLABELLED The field of ophthalmology has a number of unique features compared with other medical and surgical specialties regarding clinical workflow and data management. This has important implications for the design of electronic health record (EHR) systems that can be used intuitively and efficiently by ophthalmologists and that can promote improved quality of care. Ophthalmologists often lament the absence of these specialty-specific features in EHRs, particularly in systems that were developed originally for primary care physicians or other medical specialists. The purpose of this article is to summarize the special requirements of EHRs that are important for ophthalmology. The hope is that this will help ophthalmologists to identify important features when searching for EHR systems, to stimulate vendors to recognize and incorporate these functions into systems, and to assist federal agencies to develop future guidelines regarding meaningful use of EHRs. More broadly, the American Academy of Ophthalmology believes that these functions are elements of good system design that will improve access to relevant information at the point of care between the ophthalmologist and the patient, will enhance timely communications between primary care providers and ophthalmologists, will mitigate risk, and ultimately will improve the ability of physicians to deliver the highest-quality medical care. FINANCIAL DISCLOSURE(S) Proprietary or commercial interest disclosure may be found after the references.

Spectral domain optical coherence tomography findings in patients with acute syphilitic posterior placoid chorioretinopathy.

Purpose: To describe the appearance of acute syphilitic posterior placoid chorioretinitis, a rare ocular manifestation of syphilis, on spectral domain optical coherence tomography (SD OCT) both before and after treatment. Methods: Ophthalmic examination and imaging studies of 30 eyes of 19 confirmed cases were analyzed both at the time of presentation and at each follow-up visit. Patients with SD OCT and fluorescein angiography at the time of presentation, and at least three documented follow-up visits after initiation of therapy, were included in the study. Standard treatment of neurosyphilis was given to each patient, including 4 million units of penicillin G administered intravenously every 4 hours for 14 days. Results: Fundus examination and imaging studies were consistent with previous reports and confirmed the diagnosis of acute syphilitic posterior placoid chorioretinitis. In 13 eyes (43.3%), baseline SD OCT scans were performed within 1 to 2 days of presentation and revealed a small amount of subretinal fluid, disruption of the inner segment/outer segment junction, and hyperreflective thickening of the retinal pigment epithelium (RPE). All 30 eyes were again scanned between Days 7 and 9 after presentation and revealed loss of the inner segment/outer segment and OS/RPE bands, and irregular hyperreflectivity of the RPE with prominent nodular elevations but without subretinal fluid. Early disruption of the external limiting membrane and punctate choroidal hyperreflectivity were seen in 1 of the 30 eyes (3.3%) and 14 of the 30 eyes (46.6%), respectively. Vision improved and the outer retinal abnormalities normalized in 28 of the 30 eyes (93.3%) after the treatment of neurosyphilis. The external limiting membrane, inner segment/outer segment band, and/or linear outer segment/RPE junction remained substantially abnormal despite treatment in 2 eyes left with 20/200 vision. Conclusion: Patients with acute syphilitic posterior placoid chorioretinitis show characteristic outer retinal abnormalities on SD OCT imaging, including disruption of the inner segment/outer segment band, nodular thickening of the RPE with loss of the linear outer segment/RPE junction, and, in some cases, loss of the external limiting membrane, accumulation of subretinal fluid, and punctate hyperreflectivity in the choroid. Vision improved and these abnormalities reversed after treatment of neurosyphilis in most of the patients. Persistently, poor vision despite treatment was associated with long-term loss or disruption of outer retinal anatomy on SD OCT.

Same-day triple therapy with photodynamic therapy, intravitreal dexamethasone, and bevacizumab in wet age-related macular degeneration.

Purpose: To report the results of same-day triple therapy with reduced fluence photodynamic therapy, intravitreal dexamethasone, and bevacizumab in patients with neovascular age-related macular degeneration. Methods: Retrospective case series. Records of patients who received same-day triple therapy with reduced fluence photodynamic therapy (25 J/cm2), intravitreal dexamethasone (200 &mgr;g), and intravitreal bevacizumab (1.25 mg) were reviewed. All patients had neovascular subfoveal age-related macular degeneration with at least 1 year of follow-up. Snellen visual acuity (VA), central macular thickness on optical coherence tomography, intraocular pressure, and endophthalmitis occurrence were recorded. Results: The 31 patients were observed for a mean of 13.7 months. In all patients, mean baseline VA was 20/80 and vision at final follow-up was 20/60 (P = 0.69). In patients who received previous treatment for exudative age-related macular degeneration (n = 18), mean baseline VA was 20/100 and vision at final follow-up (mean, 13.7 months) was 20/100 (P = 0.31). In treatment-naïve patients (n = 13), mean baseline VA was 20/60 and vision at final follow-up (mean, 13.5 months) was 20/40 (P = 0.31). In all patients, mean central macular thickness was 293 &mgr;m at baseline and 245 &mgr;m at final follow-up (P = 0.053). In previously treated patients (n = 18), mean central macular thickness was 325 &mgr;m at baseline and 265 &mgr;m at final follow-up (P = 0.10). In treatment-naïve patients, mean central macular thickness was 249 &mgr;m at baseline (n = 13) and 218 &mgr;m at final follow-up (P = 0.34). Previously treated patients required more antivascular endothelial growth factor injections (mean = 3.6) than treatment-naïve patients (mean = 0.8), but the mean number of repeat triple therapy treatments was 0.3 in both groups. Changes in intraocular pressure and endophthalmitis were not observed during follow-up. Conclusion: Same-day triple therapy maintained VA and decreased macular thickness in patients with and without previous antivascular endothelial growth factor therapy. Triple therapy may reduce the number of antivascular endothelial growth factor injections in some patients and stabilize vision in some patients not responding to antivascular endothelial growth factor therapy.