Eric Chen

Endophthalmitis after intravitreal injection: the importance of viridans streptococci.

Purpose: To determine the rate of postinjection endophthalmitis and compare microbial etiology and outcomes in office-based injection-related endophthalmitis versus those acquired after operating room procedures. Methods: Retrospective, observational case series. Consecutive cases of endophthalmitis seen at Retina Consultants of Houston between July 2000 and July 2010 were classified as postsurgical or post-intravitreal injection. Cases secondary to glaucoma surgery, trauma, and endogenous sources were excluded. Main study measures were incidence of endophthalmitis, microbiology results, and visual outcomes. Results: In all, 109 cases of endophthalmitis were identified: 88 postsurgical and 21 post-intravitreal injection (3 from clinical trials and 5 from outside ophthalmologists). A total of 33,580 intravitreal injections were performed at Retina Consultants of Houston (endophthalmitis rate = 0.04%, 13 of 33,580; 95% confidence interval, 0.02-0.07%). The most common organisms isolated overall were coagulase-negative staphylococci, while viridans streptococci, a component of human oral flora, was identified over three times more often in the postinjection group compared with the postsurgical group. Compared with all other culture-positive cases related to intravitreal injection, postinjection endophthalmitis secondary to viridans streptococci presented much more rapidly (P < 0.001) and final visual outcomes were much worse (P = 0.004) Conclusion: Although the overall risk of postinjection endophthalmitis is low, viridans streptococci were identified over three times more frequently in postinjection cases compared with postsurgical cases and these cases had much worse clinical outcomes. The office-based setting for intravitreal injections may lead to a higher risk for infection from oral pathogens.

Super-dose Anti-VEGF (SAVE) Trial: 2.0 mg Intravitreal Ranibizumab for Recalcitrant Neovascular Macular Degeneration–Primary End Point

PURPOSE To determine whether a higher dose of intravitreal ranibizumab could improve the anatomy and best-corrected visual acuity (BCVA) in eyes with neovascular age-related macular degeneration (AMD) with persistent disease activity despite monthly intravitreal anti-vascular endothelial growth factor (VEGF) injections. DESIGN Phase I to II multicenter, open-label, controlled clinical trial. PARTICIPANTS Eighty-seven patients with recalcitrant neovascular AMD, defined as having leakage on fundus fluorescein angiography or spectral domain optical coherence tomography (SD-OCT) despite monthly anti-VEGF injections. METHODS Patients were treated with 2.0-mg ranibizumab injections monthly for 3 doses and monitored with Early Treatment Diabetic Retinopathy Study (ETDRS) 4-m refractions, clinical examinations, and SD-OCT. MAIN OUTCOME MEASURES The mean change in baseline visual acuity (VA), the percentage of patients who experienced a loss or gain of 15 or more letters in ETDRS BCVA, the mean change in central retinal thickness, and the incidence of adverse events. RESULTS Eighty-seven patients with an average of 24 injections before enrollment and a mean of 10.4 injections in the preceding 12 months had a mean refracted VA of 69.2 ETDRS letters (20/41 Snellen) and a mean central subfield of 422 μm at baseline. Mean VA gain over baseline was +2.5 letters at day 7 (n = 82), +3.7 letters at month 1 (n = 87), +3.9 letters at month 2 (n = 87), and +3.3 letters at month 3 (20/36 Snellen; P = 0.001; n = 86). Anatomic outcomes showed a mean optical coherence tomography central subfield thickness improvement from baseline of -48.4 μm at day 7 (n = 84), -37.5 μm at month 1 (n = 87), -42.4 μm at month 2 (n = 85), and -33.1 μm at month 3 (P = 0.01; n = 86). CONCLUSIONS Intravitreal injections of 2.0 mg ranibizumab led to statistically significant VA gains and anatomic improvement in patients with persistent intraretinal, subretinal, or subretinal pigment epithelial fluid during a previous regimen of chronic monthly 0.5-mg ranibizumab injections.

Hypotony after 25-gauge vitrectomy using oblique versus direct cannula insertions in fluid-filled eyes.

Purpose: To compare intraocular pressure (IOP) and rates of postoperative hypotony with 25-gauge pars plana vitrectomy (PPV) without tamponade using oblique versus direct cannula insertions. Methods: A prospective consecutive series of eyes that underwent 25-gauge PPV without tamponade using an oblique cannula insertion technique was compared with a historical consecutive series of eyes that underwent 25-gauge PPV without tamponade using direct cannula insertions. IOP was recorded before surgery, on postoperative day 1, and on postoperative week 1. Results: Ninety-five eyes had 25-gauge PPV without tamponade, 55 with oblique cannula insertions and 40 with direct insertions. With oblique insertions, there was no statistically significant difference between mean IOPs measured before surgery, on postoperative day 1, and on postoperative week 1. Only 1 (1.8%) of the 55 eyes had hypotony (IOP, ≤5 mmHg) on postoperative day 1. With direct insertions, mean postoperative day 1 IOP was significantly lower than mean preoperative IOP (P = 0.009). Mean preoperative and postoperative week 1 IOPs were similar. Four (10%) of 40 eyes had hypotony on postoperative day 1. Conclusions: Oblique cannula insertions may be superior to direct cannula insertions for lowering rates of absolute and relative postoperative day 1 hypotony in 25-gauge PPV without tamponade.

Streptococcus mitis endophthalmitis presenting as frosted branch angiitis after intravitreal pegaptanib sodium injection.

An 80-year-old woman presented with endophthalmitis and a frosted branch angiitis-like picture following intravitreal injection of pegaptanib sodium for age-related macular degeneration. After vitreous tap and injection of antibiotics, the patient underwent vitrectomy because her clinical condition worsened. Cultures grew Streptococcus mitis, and the patients visual acuity stabilized at hand motions following unsuccessful repair of a retinal detachment complicated by proliferative vitreoretinopathy. Because S. mitis can cause an endophthalmitis that presents as frosted branch angiitis, it must be considered in the differential diagnosis of patients who present with frosted branch angiitis.

SAVE (Super-dose Anti-VEGF) Trial: 2.0 mg Ranibizumab for Recalcitrant Neovascular Age-Related Macular Degeneration: 1-Year Results

OBJECTIVES To assess durability of visual and anatomic gains with 2.0 mg ranibizumab in recalcitrant neovascular age-related macular degeneration (AMD). METHODS Phase I-II trial of 88 patients with recalcitrant neovascular AMD treated as needed every 4 (cohort A) or 6 weeks (cohort B) following three monthly doses. ETDRS refraction and spectral-domain OCT-guided as-needed re-treatments. RESULTS Seventy-nine patients completed the 12-month endpoint and were given 11.6 (cohort A) and 8.6 (cohort B) mean treatments. Mean best corrected visual acuity gains of 4.1 letters following three monthly doses were sustained for 12 months for both cohorts. Anatomic improvements were sustained for 12 months for cohort A, but not for cohort B; cohort B demonstrated a gradual increase in mean central retinal thickness (P = .03). CONCLUSION Visual and anatomic gains achieved with 2.0 mg ranibizumab in recalcitrant neovascular AMD were sustained for 1 year with monthly treatment. In comparison, anatomic gains were diminished with less than monthly treatment.

ENDOPHTHALMITIS AFTER INTRAVITREAL INJECTION: Role of Prophylactic Topical Ophthalmic Antibiotics.

Purpose: To determine the rate of postintravitreal injection endophthalmitis and to assess microbiological features and outcomes with and without the use of peri-intravitreal injection topical ophthalmic antibiotics. Methods: Consecutive series of endophthalmitis cases retrospectively identified after intravitreal injection at a multicenter, retina-only referral practice (Retina Consultants of Houston) from January 1, 2011 to December 31, 2014. Prophylactic peri-intravitreal injection topical antibiotics were routinely used during the initial 12-month period (January 1, 2011–December 31, 2011) and not used in the final 24-month period (January 1, 2013–December 31, 2014). Main outcome measures were incidence of endophthalmitis, microbiology results, treatment strategies, and visual outcomes. Results: Of 90,339 intravitreal injections, 30 cases of endophthalmitis were identified (endophthalmitis rate = 0.033%; 95% confidence interval, 0.021–0.045%; or approximately 1 of 3,011 intravitreal injections). The most common organisms isolated were coagulase-negative staphylococci (n = 10, 33%), followed by Streptococcus mitis (n = 2, 7%). Fourteen cases (47%) were culture negative. Peri-intravitreal injection topical antibiotic prophylaxis did not decrease the rate of endophthalmitis (0.035% [95% CI, 0.007–0.064%] with antibiotic use versus 0.021% [95% CI, 0.008–0.033%] without antibiotic use; P = 0.261). Conclusion: The risk of endophthalmitis after intravitreal injection remains low, with coagulase-negative staphylococci and Streptococcus mitis the most common bacterial isolates identified. Prophylactic peri-intravitreal injection topical ophthalmic antibiotic use did not decrease the endophthalmitis rate.

Comparison of spectral-domain and time-domain optical coherence tomography in the detection of neovascular age-related macular degeneration activity

Purpose: To compare the sensitivity of commonly used time-domain (TD-OCT) and spectral-domain optical coherence tomography platforms and scanning modalities in the management of neovascular age-related macular degeneration in a population with a high prevalence of exudative disease activity. Methods: Fifty consecutive patients within the prospective SAVE (Super-dose Anti-Vascular Endothelial growth factor) trial, which analyzed the utility of 2.0 mg intravitreal ranibizumab for the treatment of recalcitrant neovascular age-related macular degeneration, were enrolled in a comparison trial of 3 different optical coherence tomography (OCT) platforms. Stratus TD-OCT radial scan (Carl Zeiss Meditec, Inc) was compared with 3 Heidelberg Spectralis Heidelberg Retinal Angiograph+OCT (Heidelberg Engineering) acquisition settings (radial, 7-line raster, volumetric) and 2 Cirrus high definition (HD)-OCT (Carl Zeiss Meditec, Inc) acquisition settings (5-line raster, volumetric). Results: Using every imaging platform and acquisition setting, evidence of exudative disease activity was positively identified in 163 of 191 patient visits (85.3%). Intraretinal cysts were identified in 83 of 191 visits (43.5%), and subretinal fluid was identified in 116 of 191 visits (60.7%). Of these positive visits, the Stratus TD-OCT radial scanning technology demonstrated a significantly lower rate of detection (71.8%) when compared with the Spectralis HRA+OCT spectral domain scanning modalities (radial 87.1%, P < 0.001; 7-line raster 92.0%, P < 0.001; volumetric 94.5%, P < 0.001) or the Cirrus HD-OCT spectral domain scanning modalities (5-line raster 81.6%, P = 0.001; volumetric 92.0%, P < 0.001). Intraretinal cysts and subretinal fluid were identified in 83 visits (43.5%) and 116 visits (60.7%), respectively, with 36 eyes (18.8%) having fluid in both locations. No individual imaging modality demonstrated a diagnostic advantage for detecting subretinal fluid versus intraretinal cysts (e.g., Cirrus volume detected 86.7% of intraretinal cysts and 88.8% of subretinal fluid, P = 0.33). Conclusion: In this neovascular age-related macular degeneration patient population, spectral-domain ocular coherence tomography was a superior diagnostic tool when compared with TD-OCT, with each spectral domain platform and acquisition setting identifying significantly more exudative disease activity. The two spectral domain platforms (Cirrus and Spectralis) were not directly compared because identical image acquisition parameters were not used. No individual imaging modality demonstrated a diagnostic advantage for detecting subretinal fluid versus intraretinal cysts.

Incidence and clinical features of post-injection endophthalmitis according to diagnosis

Purpose To compare the incidence and clinical features of endophthalmitis after intravitreal antivascular endothelial growth factor (VEGF) therapy for diabetic eye disease, neovascular age-related macular degeneration (AMD) and retinal vein occlusion (RVO). Methods Multicentre, retrospective, consecutive case–control study. All patients treated with intravitreal bevacizumab, ranibizumab or aflibercept for diabetic eye disease, neovascular AMD or RVO between 1 January 2009 and 30 September 2013 at three retina practices were included in this study. The total number of anti-VEGF injections administered for the three indications was calculated using billing records. Endophthalmitis cases were identified using both endophthalmitis log sheets and billing records. Patient charts were reviewed to confirm that endophthalmitis was directly related to anti-VEGF injection and to record clinical features and culture results. Results During the study period, a total of 353 978 intravitreal anti-VEGF injections were performed. Presumed infectious endophthalmitis occurred in 119 of 296 017 injections performed for neovascular AMD (1/2487, 0.040%), 12 of 24 541 for diabetic eye disease (1/2045, 0.049%) and 4 of 32 418 for RVO (1/8104, 0.012%). χ2 analysis found endophthalmitis rates to be higher in diabetic eye disease compared with RVO (p=0.010) and higher in neovascular AMD compared with RVO (p=0.014), while diabetic eye disease and neovascular AMD (p=0.517) had similar rates. The average age of the overall neovascular AMD patient population (81.9 years) was significantly older than the diabetic eye disease (64.7 years, p<0.001) and RVO (73.4 years, p<0.001) populations. Conclusions Endophthalmitis rates appear to be lower in eyes with RVO compared with diabetic eye disease and neovascular AMD, possibly due to impaired immunity in diabetics and waning immunity in the generally older AMD population.

THE ASSOCIATION OF EPIRETINAL MEMBRANE WITH MACULAR HOLE FORMATION AFTER RHEGMATOGENOUS RETINAL DETACHMENT REPAIR

Purpose: To describe the clinical and optical coherence tomography findings associated with the development of full-thickness macular holes after rhegmatogenous retinal detachment (RRD) repair. Methods: Retrospective, interventional case series. All patients who developed full-thickness macular holes after successful RRD repair from 3 clinical practices were reviewed. All cases of combined/simultaneous full-thickness macular hole and RRD were excluded. The main outcome measure was the presence of an epiretinal membrane at time of diagnosis of macular hole. Results: Twenty-five full-thickness macular holes were diagnosed after successful retinal detachment repair. Surgical approach to RRD repair included pneumatic retinopexy (6, 24%), scleral buckle alone (5, 20%), pars plana vitrectomy only (8, 32%), and combined scleral buckle and pars plana vitrectomy (6, 24%). The preceding RRD involved the macula in 19 patients (76%) before the formation of the macular hole. The median time to full-thickness macular hole diagnosis after RRD repair was 63 days (range, 4–4,080 days). An epiretinal membrane was present in all 25 (100%) macular holes. Two macular holes (8%) spontaneously closed, whereas the other 23 (92%) were successfully closed with a single surgical procedure. Mean visual acuity improved by approximately 5 lines to 20/72 (range, 20/20 to counting fingers at 1 foot) from 20/240 (range, 20/30 to hand motions) after macular hole repair (P < 0.0001). Conclusion: Full-thickness macular hole formation can occur after all types of RRD repair and is associated with an epiretinal membrane. The epiretinal membrane may play a role in the pathogenesis of secondary macular hole formation after RRD repair.

Cytomegalovirus retinitis after treatment with intravitreal triamcinolone acetonide in an immunocompetent patient.

PURPOSE To describe a case of cytomegalovirus (CMV) retinitis following intravitreal triamcinolone acetonide (IVTA) in an immunocompetent patient. METHODS A 77-year-old man with a history of diabetes mellitus developed retinal whitening with a vasculitis 6 weeks after receiving IVTA in the left eye. A vitreous biopsy was performed. RESULTS Polymerase chain reaction was positive for CMV (419,000 copies/mL). A complete medical evaluation, including a negative test for human immunodeficiency virus, showed no systemic evidence of immunosuppression except for a highly elevated hemoglobin A1C level. CONCLUSION CMV retinitis may be a rare complication of IVTA, possibly due to local ocular immunosuppression from the steroid medication. Poorly controlled diabetes mellitus may have contributed to this development.