Sunir J. Garg

Complications of intravitreal injections.

Purpose of review Over the past few years, the results of many studies have highlighted the risks and benefits of intravitreal injection of a number of medications, the most common being triamcinolone, antivascular endothelial growth factor (VEGF) agents, antibiotics, antivirals, antifungals, and methotrexate. The purpose of this review is to highlight the complications associated with these injections. Recent findings Elevated intraocular pressure and glaucoma are the most common complications of intraocular triamcinolone. There is also an increased incidence of cataract formation/progression over time. The immunosuppressive effect of triamcinolone does not appear to increase the risk of endophthalmitis. Recent reports suggest that intravitreal anti-VEGF injections have a low complication rate. Similarly, antimicrobials also have low rates of injection-associated complications. Summary Intravitreal injections play a critical role in daily ophthalmic practice. The overall risk of endophthalmitis and retinal detachment appears to be low and most of the commonly used drugs are well tolerated, even with repeat injection. Further long-term studies need to be performed to elucidate ways of increasing the safety of these procedures and medications.

Outcomes and Risk Factors Associated with Endophthalmitis after Intravitreal Injection of Anti- Vascular Endothelial Growth Factor Agents.

OBJECTIVE To describe outcomes of and risk factors for endophthalmitis after intravitreal anti-vascular endothelial growth factor (VEGF) injection. DESIGN Single-center, consecutive, case series and retrospective case-control study. PARTICIPANTS Between January 1, 2009, and May 31, 2010, 16 vitreoretinal surgeons administered a total of 27 736 injections. During this period, 23 cases of presumed infectious endophthalmitis occurred. Each surgeon used his own preferred injection technique. INTERVENTION Vitreous or aqueous tap, or both, with intravitreal antibiotic injection and subsequent topical antibiotic and steroid drops. MAIN OUTCOME MEASURES Visual acuity, bladed lid speculum use, conjunctival displacement, hemisphere of injection, bevacizumab versus ranibizumab, and infectious organism. RESULTS Seven of 23 cases had positive culture results; 3 grew coagulase-negative Staphylococcus. All cases had pain and vitritis on average 3.4 days (range, 1-6 days) after injection, with no difference between culture-positive and culture-negative groups. Eighteen (78%) of 23 cases had a hypopyon. Fifteen of 23 cases returned to baseline vision (±2 lines) within 3 months. Neither lid speculum use (0.10% vs. 0.066% in the no-use group; P = 0.27), conjunctival displacement (0.11% vs. 0.076% in the no-displacement group; P = 0.43), hemisphere of injection (0.11% superior vs. 0.079% inferior; P = 0.56), or bevacizumab versus ranibizumab (0.11% vs. 0.066%; P = 0.21) affected risk. Analysis of only culture-positive results yielded similar results. There was no statistically significant difference between the proportion of culture-negative cases after bevacizumab injection (83%) versus ranibizumab injection (55%; P = 0.13). CONCLUSIONS Most patients in whom presumed infectious endophthalmitis develop after anti-VEGF injection regained baseline vision after treatment. Bladed lid speculum use, conjunctival displacement, hemisphere of injection, and type of anti-VEGF agent did not affect risk. No difference in culture-negative endophthalmitis rates was detected after bevacizumab versus ranibizumab injection. Neither the presence of pain, vitritis, decreased vision, hypopyon, nor the interval between injection and development of symptoms differentiate culture-positive from culture-negative cases. Because a subgroup of patients had poor outcomes, a low threshold for vitreous tap with intravitreal antibiotic injection may be warranted. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The role of topical antibiotic prophylaxis to prevent endophthalmitis after intravitreal injection.

OBJECTIVE To compare the incidence of endophthalmitis after intravitreal injection with and without topical postinjection antibiotic prophylaxis. DESIGN Retrospective case-control study. PARTICIPANTS All patients treated with intravitreal injection of ranibizumab, bevacizumab, or aflibercept for a variety of retinal vascular diseases at a single, large retina practice between January 1, 2009, and October 1, 2012, were included. METHODS The total numbers of patients and injections were determined from a review of billing code and practice management records. Endophthalmitis cases were determined from billing records and from an infection log. All cases of endophthalmitis were confirmed with chart review. A 28-month period when topical antibiotics were prescribed after intravitreal injection was compared with a 9-month period when topical antibiotics were not prescribed. Patients treated during an 8-month transition period were excluded to allow for the conversion of antibiotic prescription practices. MAIN OUTCOME MEASURES Incidence of endophthalmitis, visual acuity outcomes, and microbial spectrum. RESULTS During the study period, a total of 117 171 intravitreal injections were performed (57 654 injections during the topical antibiotic period, 24 617 during the transition period, and 34 900 during the no-antibiotic period), with a total of 44 cases of suspected endophthalmitis (0.038%; 1 in 2663 injections), 17 of which showed culture-positive results (0.015%; 1 in 6892 injections). During the 28-month topical antibiotic period, there were 28 cases of suspected endophthalmitis (0.049%; 1 in 2059 injections), 10 of which showed culture-positive results (0.017%; 1 in 5765 injections). During the 9-month no-antibiotic period, there were 11 cases of suspected endophthalmitis (0.032%; 1 in 3173 injections), 4 of which showed culture-positive results (0.011%; 1 in 8725 injections). Topical antibiotic use was associated with a trend toward increased risk of suspected endophthalmitis (odds ratio [OR], 1.54; 95% confidence interval [CI], 0.77-3.10) and culture-positive endophthalmitis (OR, 1.51; 95% CI, 0.47-4.83). CONCLUSIONS The incidence of endophthalmitis after intravitreal injection is low. Using postinjection topical antibiotic drops does not reduce the risk of endophthalmitis developing and is associated with a trend toward higher incidence of endophthalmitis.

Changes in Antibiotic Resistance Patterns of Conjunctival Flora Due to Repeated Use of Topical Antibiotics after Intravitreal Injection

OBJECTIVE To determine the effect of repeated intermittent use of topical antibiotics after intravitreal injections on conjunctival bacterial flora and antibiotic resistance. DESIGN Cross-sectional case-control study. PARTICIPANTS AND CONTROLS A total of 80 eyes of 40 patients were enrolled (40 study eyes, 40 control eyes). Patients were enrolled with unilateral exudative age-related macular degeneration who had received at least 3 prior intravitreal injections with use of postinjection topical antibiotics. Patients had received an average of 7 (range, 3-13) intravitreal injections before enrollment. METHODS At the time of enrollment, the inferior fornix of the treated eye was swept with a culture swab before use of povidone iodine; the inferior fornix of the fellow eye was also cultured and served as a control. The culture and sensitivity data from the study and control eyes were analyzed. MAIN OUTCOME MEASURES The rate of antibiotic resistance among the conjunctival bacterial flora of the study eyes and control eyes. RESULTS A total of 80 eyes of 40 patients were enrolled in the study; 29 patients used trimethoprim/polymyxin B drops, and 11 patients used fluoroquinolone drops after each injection. A total of 58 bacterial colonies were isolated from 50 eyes. There were no significant differences in bacterial species or culture positivity rates between study and control eyes. Coagulase-negative staphylococcus accounted for 41 of the 58 bacterial colonies (71%). There was a 63.6% resistance rate to fluoroquinolones among study eyes compared with 32.1% among control eyes (P < 0.05). In the subset of 11 study eyes using fluoroquinolone drops for 4 days after injection, there was an 87.5% resistance rate compared with 25.0% in matched control eyes (P = 0.04). There was no significant difference in trimethoprim resistance rates between study and control eyes: Four of 14 study eyes (28.6%) showed resistance compared with 5 of 18 control eyes (27.7%) (P = 1.0). CONCLUSIONS Use of fluoroquinolone drops after intravitreal injection leads to increased rates of resistance among conjunctival flora. Repeated use of topical fluoroquinolones after intravitreal injections may have a detrimental effect on eye health by breeding resistance in the bacterial flora.

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.

Retinal pigment epithelial tears after intravitreal bevacizumab injection for exudative age-related macular degeneration

Purpose:  To determine the incidence of and the risk factors for the development of retinal pigment epithelial (RPE) tears after intravitreal bevacizumab (Avastin) injection for the treatment of exudative age‐related macular degeneration (AMD).

The competency of pars plana vitrectomy incisions: a comparative histologic and spectrophotometric analysis.

PURPOSE To compare the relative competency of pars plana vitrectomy (PPV) sclerotomies. DESIGN Laboratory investigation. METHODS PPV was performed in human cadaveric eyes using 20-gauge (20 G), 23-gauge (23 G), and 25-gauge (25 G) instrumentation. India ink was applied over a sclerotomy site while the intraocular pressure was varied. The presence of India ink particles (IIPs) along incisions was evaluated by histologic analysis. Spectrophotometric absorbance levels of vitreous aspirates were measured. RESULTS PPV was performed in a control eye and two eyes, each using standard 20 G, standard 23 G, perpendicular 25 G, and beveled 25 G instrumentation incisions. IIPs were not detected in the 20 G incisions either on histology or by spectrophotometry. IIPs were detected along the entire incision length in one of two eyes with 23 G sclerotomies and confirmed by spectrophotometry. IIPs were detected along the entire incision length in one of two eyes with 25 G perpendicular sclerotomies and confirmed by spectrophotometry in both eyes. IIPs were noted partially along the length in one of the two beveled 25 G eyes, but not detected in either eye by spectrophotometry. CONCLUSIONS During the early postoperative period, sutureless vitrectomy incisions may allow entry of ocular surface fluid. These findings may provide a pathophysiologic mechanism for the reported increased risk of endophthalmitis in small-gauge vitrectomy surgery.

Conjunctival Flora Antibiotic Resistance Patterns After Serial Intravitreal Injections Without Postinjection Topical Antibiotics

PURPOSE To report conjunctival bacterial flora antibiotic resistance patterns after serial intravitreal injections performed using a povidone-iodine preparation without the use of preinjection or postinjection topical antibiotics. DESIGN Prospective, interventional case series. METHODS SETTING Single-center clinical practice in Pennsylvania. STUDY POPULATION Thirteen eyes of 13 treatment-naïve patients undergoing serial intravitreal anti-vascular endothelial growth factor (VEGF) injections for exudative age-related macular degeneration or macular edema attributable to retinal vein occlusion. INTERVENTION Conjunctival cultures from the treatment eye were performed prior to each injection preparation. A minimum of 3 monthly conjunctival cultures were obtained per eye over the course of the study. Ocular surface preparation consisted of topical anesthetic and povidone-iodine 5% without the use of preinjection or postinjection topical antibiotics. MAIN OUTCOME MEASURES Conjunctival flora growth patterns and antibiotic resistance patterns to several common antibiotics tested over the course of the study. RESULTS A total of 48 cultures were performed with a 77% culture positivity rate. Over the course of the serial conjunctival cultures in each patient, there was no evidence for emergence of resistant bacteria to any of the tested antibiotics (including fluoroquinolones and azithromycin) or significant alteration from baseline conjunctival flora. Of the 47 bacterial isolates, the most commonly isolated organism was coagulase-negative Staphylococcus both at baseline (73%) and following serial intravitreal injections (78%, P = .73). CONCLUSIONS Ocular surface preparation for intravitreal injection using povidone-iodine 5% alone in the absence of postinjection topical antibiotics does not appear to promote bacterial resistance or a discernible change in conjunctival flora.

Management of Thick Submacular Hemorrhage With Subretinal Tissue Plasminogen Activator and Pneumatic Displacement for Age-Related Macular Degeneration

PURPOSE To evaluate the outcome of pars plana vitrectomy, subretinal tissue plasminogen activator (t-PA) infusion and intraocular gas tamponade with and without postsurgical antivascular endothelial growth factor (VEGF) injection for thick submacular hemorrhage due to exudative age-related macular degeneration (AMD). DESIGN Retrospective, comparative, interventional case series. METHODS setting: 2 retina referral centers. The patient population included 101 eyes of 101 patients with neovascular AMD and thick submacular hemorrhage who underwent surgical displacement of the hemorrhage with or without postoperative anti-VEGF injections. Main outcome measures included degree of blood displacement, best and final postoperative visual acuity (VA), and adverse events. Snellen acuity was converted to logMAR for statistical analysis. RESULTS All patients were followed for a minimum of 3 months (mean, 15.3 months, range, 3-70 months). In 83 (82%) of 101 eyes, the procedure resulted in complete hemorrhage displacement from the fovea. Mean preoperative VA was 20/2255 (2.05 logMAR). The acuity significantly improved to 20/893 (1.65 logMAR) at month 1 (P < 0.001) at month 1; 20/678 (1.53 logMAR) at month 3 (P < 0.001), and 20/1150 (1.76 logMAR) at month 12 (P = 0.002). Best postoperative visual acuity improved by at least 1 line in 83 (82%) of 101 eyes, and 19.6% of eyes gained 3 lines or more at month 3. The visual acuity of the group of eyes that received postoperative anti-VEGF injection (n = 39) showed greater visual acuity improvement 6 months postoperatively compared to the group of eyes that did not receive postoperative anti-VEGF. Postoperative complications included vitreous hemorrhage in 2 eyes, rhegmatogenous retinal detachment in 4 eyes, and recurrent thick subretinal hemorrhage in 6 eyes. CONCLUSIONS Vitrectomy with subretinal t-PA injection and gas tamponade was found to be relatively effective for displacement of thick submacular hemorrhage with a significant improvement in visual acuity. There is a loss of acuity over time; the addition of postoperative anti-VEGF therapy may help maintain the visual acuity gains.

Optical coherence tomography of chronic solar retinopathy.

PURPOSE To describe the optical coherence tomographic findings in eight eyes of four patients with chronic solar retinopathy. All patients had a history of sun gazing months to years prior to presentation. DESIGN Retrospective case series. METHODS Patients were examined using biomicroscopy performed by two or more experienced vitreoretinal specialists. All eight eyes had optical coherence tomography performed at the time of initial examination. RESULTS All patients had a history of sun gazing and decreased vision in both eyes. On biomicroscopy, all eyes had a small, irregularly-shaped lamellar defect in the foveal center. No posterior vitreous detachment was present in any eye. Optical coherence tomography revealed a hyporeflective space at the level of the outer neurosensory retina and retinal pigment epithelium in all eyes. CONCLUSION Optical coherence tomography demonstrates a characteristic hyporeflective space in the outer retina in patients with chronic solar retinopathy. These findings correlate with the histopathology of this condition and may be a useful clinical tool in confirming its diagnosis.