Peter J. Kertes

Incidence of Endophthalmitis and Use of Antibiotic Prophylaxis after Intravitreal Injections

PURPOSE To report the incidence of endophthalmitis in association with different antibiotic prophylaxis strategies after intravitreal injections of anti-vascular endothelial growth factors and triamcinolone acetonide. DESIGN Retrospective, comparative case series. PARTICIPANTS Fifteen thousand eight hundred ninety-five intravitreal injections (9453 ranibizumab, 5386 bevacizumab, 935 triamcinolone acetonide, 121 pegaptanib sodium) were reviewed for 2465 patients between January 5, 2005, and August 31, 2010. The number of injections was determined from billing code and patient records. METHODS The indications for injection included age-related macular degeneration, diabetic macular edema, central and branch retinal vein occlusion, and miscellaneous causes. Three strategies of topical antibiotic prophylaxis were used by the respective surgeons: (1) antibiotics given for 5 days after each injection, (2) antibiotics given immediately after each injection, and (3) no antibiotics given. MAIN OUTCOME MEASURES The primary outcome measures were the incidence of culture-positive endophthalmitis and culture-negative cases of suspected endophthalmitis. RESULTS Nine eyes of 9 patients with suspected endophthalmitis after injection were identified. Three of the 9 cases had culture-positive results. The overall incidence of endophthalmitis was 9 in 15 895. The incidence of culture-negative cases of suspected endophthalmitis and culture-proven endophthalmitis after injection was 6 in 15 895 and 3 in 15 895, respectively. Taking into account both culture-positive endophthalmitis and culture-negative cases of suspected endophthalmitis, the incidence per injection was 5 in 8259 for patients who were given antibiotics for 5 days after injection, 2 in 2370 for those who received antibiotics immediately after each injection, and 2 in 5266 who received no antibiotics. However, if considering culture-proven endophthalmitis alone, the use of topical antibiotics, given immediately or for 5 days after injection, showed lower rates of endophthalmitis compared with those without postinjection antibiotics. The risk of endophthalmitis after intravitreal injection varied among agents that were used. Among the 9 cases of clinically suspected endophthalmitis, regardless of prophylactic strategies used, the incidence of endophthalmitis per injection was 2 in 935 for triamcinolone acetonide, 3 in 9453 for ranibizumab, and 4 in 5386 for bevacizumab. CONCLUSIONS The overall rate of intravitreal injection-related endophthalmitis is greater with the use of topical antibiotics, given immediately or for 5 days after the injection, compared with no antibiotics.

Internal resection of posterior uveal melanomas

AIMS To evaluate the safety and efficacy of internal resection in the treatment of malignant melanoma of the choroid. METHODS 32 consecutive patients with histopathologically proved malignant choroidal melanomas were treated with internal resection. 29 of the 32 (90.6%) tumours were within 2 disc diameters of the optic nerve or fovea. The surgery was performed at two university centres by one of the authors. Follow up was between 1 and 85 months (mean 40.1 months). RESULTS Three patients developed distant metastases and died of malignant melanoma (metastatic and mortality rate 9.4%). In one case, distant metastases developed in association with an intraocular recurrence. There have been no other intraocular recurrences. The most common postoperative complication was vitreous haemorrhage, which occurred in 12 patients (37.5%); cataract occurred in eight eyes; and three patients developed retinal detachment postoperatively. Three of the operated eyes have been enucleated (9.4%); a total of four (12.5%) have lost light perception. 10 patients (31.2%) had visual acuities of 6/60 or better and 18 of 32 (56.3%) were between 6/120 and light perception. CONCLUSION These data suggest that the internal resection of posterior uveal melanomas is a reasonable globe saving management option. This treatment modality is particularly well suited to elevated tumours in close proximity to the optic nerve or fovea.

Antibiotic Resistance of Ocular Surface Flora With Repeated Use of a Topical Antibiotic After Intravitreal Injection

IMPORTANCE Treatment with intravitreal (IVT) injections has increased during the last several years as evidence has accumulated demonstrating the efficacy of anti-vascular endothelial growth factor agents in the treatment of neovascular age-related macular degeneration (AMD) and various retinal vascular diseases. Although IVT injections are generally safe, infectious endophthalmitis is a rare but devastating complication, and the risk of morbidity and vision loss from endophthalmitis is high. OBJECTIVE To examine the change in antibiotic resistance of ocular surface flora with repeated prophylactic use of antibiotics after IVT injection for AMD. DESIGN AND SETTING Prospective, nonrandomized cohort study in 2 tertiary academic hospitals. PARTICIPANTS Patients 65 years and older with newly diagnosed AMD were recruited by 7 retinal specialists from July 1, 2010, through December 31, 2011. INTERVENTION The study group received topical moxifloxacin hydrochloride for 3 days after each monthly IVT injection. MAIN OUTCOME MEASURE Resistance to moxifloxacin and ceftazidime in cultured isolates at baseline and monthly for 3 months by change in minimal inhibitory concentration (MIC) of culture isolates was studied. RESULTS The study group consisted of 84 patients, and the control group had 94 patients. In the study group, the baseline adjusted MIC increased (from 1.04 to 1.25 μg/mL; P = .01) as did the MIC for 50% of isolates (MIC50) (from 0.64 to 1.00 μg/mL) and the MIC for 90% of isolates (MIC90) (from 0.94 to 4.00 μg/mL). In both groups, the culture-positive rate did not change significantly when adjusted for baseline. No significant change was found in the MIC level, culture-positive rate, MIC50 level, and MIC90 level in the control group. Subgroup analysis found diabetes mellitus to be noncontributory to both the MIC and culture-positive rate. No endophthalmitis or adverse events were reported. CONCLUSIONS AND RELEVANCE Repeated use of topical moxifloxacin after IVT injection significantly increases antibiotic resistance of ocular surface flora. We recommend that routine use of prophylactic antibiotics after IVT injection be discouraged. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01181713.

Alterations in the Intraocular Cytokine Milieu after Intravitreal Bevacizumab

PURPOSE Several complications after intravitreal bevacizumab (IVB) treatment have been described including tears of the retinal pigment epithelium and tractional retinal detachment. The etiology of these complications remains unclear. The purpose of this study was to characterize changes in the intraocular levels of inflammatory cytokines after IVB as a possible explanation for these complications. METHODS Twenty-nine patients with proliferative diabetic retinopathy (PDR) undergoing pars plana vitrectomy (PPV) for vitreous hemorrhage (VH) with IVB pretreatment were prospectively enrolled. Aqueous humor samples were taken at the time of IVB pretreatment and approximately 1 week later at the time of PPV. Multiplex cytokine arrays were used to assay 20 different cytokines. Multivariate general linear regression was performed to determine differences in cytokine levels between the two study visits. Proportional hazards regression was performed to determine the relationship between cytokine levels at PPV and postoperative outcomes. RESULTS After treatment with IVB, vascular endothelial growth factor (VEGF) concentrations in the aqueous humor decreased (P = 0.0003), whereas the concentrations of IL-8 and transforming growth factor (TGF)-beta(2) increased after IVB (P < 0.03). The level of IL-8 at the time of PPV was associated with the occurrence of recurrent VH after surgery (hazard ratio, 1.32; P = 0.02). CONCLUSIONS Alterations in the intraocular inflammatory cytokine milieu occur after IVB injection, possibly as a compensatory mechanism in response to VEGF inhibition. The increased concentrations of inflammatory cytokines after IVB may be clinically significant and may be responsible for some of the complications after IVB.

Effectiveness of intravitreal ranibizumab for the treatment of neovascular age-related macular degeneration in a Canadian retina practice: a retrospective review

OBJECTIVE To assess the effectiveness of intravitreal ranibizumab for neovascular age-related macular degeneration (AMD) in a tertiary care retina practice and compare these results with published efficacy data from randomized clinical trials. DESIGN Nonrandomized, consecutive, single-centre, retrospective chart review analysis. PARTICIPANTS Ninety-four patients (95 eyes) with neovascular AMD. METHODS All treatment-naïve patients with neovascular AMD who received ranibizumab and for whom 1 year of follow-up was available were included in the analysis. The following information was gathered from each patients chart: age, sex, ocular history, treated eye, duration of symptoms at presentation, subtype of choroidal neovascular membrane, Snellen visual acuity at each visit, number of injections, visits, and optical coherence tomography measurements. RESULTS Subjects had a mean age of 81 (SD 7.11) years. The mean number of injections was 5.1 (SD 2.85) with a mean of 9.4 (SD 2.27) visits in the 12-month period. Overall, there was a gain of 2.88 (SD 24.6) letters in all eyes, and a loss of 2.5 (SD 23.1) letters in patients who met the visual acuity inclusion criteria for the clinical trials. Of the patients who met the inclusion criteria, 75% lost fewer than 15 letters and 11% gained more than 15 letters. CONCLUSIONS Visual outcomes in our study patients compared poorly with the clinical trials. Possibilities for the disparity include gaps in the number and frequency of follow-up visits, patient or doctor assessment fatigue, or gaps in optical coherence tomography utilization and the number of injections administered.

The use of intravitreal corticosteroids, evidence-based and otherwise.

Purpose of review To provide a current update on the use of intravitreal corticosteroids as a treatment for a variety of retinal diseases. Recent findings Pharmacokinetic studies demonstrate that a single 4 mg injection of intravitreal triamcinolone acetonide is present in the vitreous for up to 3 months. Many recent studies demonstrate a significant reduction in macular edema often with a significant improvement in vision for up to several months followed by a waning of treatment effect and recurrence of macular edema. Retreatments have been shown to be efficacious. Intravitreal triamcinolone acetonide may help lead to a reduction in subfoveal hard exudates in diffuse diabetic macular edema. It has been shown to be a more potent treatment than sub-Tenons and retrobulbar triamcinolone acetonide for persistent macular edema. It may also be a significant adjunctive treatment for choroidal neovascularization treated with photodynamic therapy. Intravitreal corticosteroid implants have also been shown to be beneficial in early trials for persistent macular edema. Summary Intravitreal triamcinolone acetonide provides a potent short-term treatment for persistent macular edema and may be a useful adjunctive treatment for choroidal neovascularization. It remains to be determined whether intravitreal corticosteroids can provide long-term visual gain or stabilization. The side-effect profile of intravitreal corticosteroids is significant with corticosteroid-induced intraocular pressure rises. With longer-term studies, the rate of posterior subcapsular cataract formation is higher than previously reported, and there is a small but potential risk of endophthalmitis.

Re-operation of idiopathic full-thickness macular holes after initial surgery with internal limiting membrane peel

Background/aims A retrospective consecutive case series to evaluate the efficacy of re-operation in patients with persistent or recurrent idiopathic full-thickness macular hole after initial surgery with internal limiting membrane peel (ILM). Methods 491 patients underwent surgery for full-thickness macular hole from January 2004 to November 2007. Fifty-five patients either did not close or reopened during the follow-up period. Thirty patients with initial ILM peel underwent repeat surgery involving vitrectomy, enlargement of ILM rhexis and gas tamponade. Results Anatomical closure rate was 88.8% for primary surgery and 46.7% (14/30) for re-operation. There was a statistically significant improvement in overall best corrected visual acuity (BCVA) from re-operation baseline BCVA (p=0.02) within 1 year. For holes that did not close after the second surgery, visual acuity did not worsen. Conclusion Re-operation has a reduced success rate of anatomical closure. However, BCVA is statistically significantly improved from re-operation baseline, so even though we cannot return vision to pre-pathological baseline, re-operation can improve on this new baseline.

Observations on the management of Coats' disease: less is more.

Background: In this article we share our experience of treating various severities of Coats’ disease and focus on optimal therapy for advanced disease. Methods: Retrospective chart review of 10 patients treated with varied techniques including intraocular surgery, cryopexy and/or laser photocoagulation. Results: Nine patients were male. At presentation the average age was 4.6 years (range 21 months–7 years), the average number of retinal quadrants involved with telangiectasia was 2.7 (range 1–4, median 3), eight of the 10 patients had retinal detachment, six of these being total, and all patients had macular involvement with either exudate or fibrosis. Average follow-up was 2.3 years (range 1–4.5 years). The best visual outcomes were observed in patients who presented with less severe disease. For example, the only four patients to maintain ambulatory vision all presented without total retinal detachment, two or fewer quadrants of retinal telangiectasia and a visual acuity better than light perception. No patient developed secondary angle closure glaucoma, and all patients have kept a cosmetically acceptable eye. Conclusion: In this limited series, visual outcomes in the setting of advanced Coats’ disease are largely dependent on disease severity and visual status at the time of presentation. Minimally invasive surgery with vitreous infusion through the pars plana, combined with external drainage of subretinal fluid together with cryotherapy and/or laser photocoagulation is sufficient to effect retinal re-attachment and prevent loss of the eye.

Canadian expert consensus: optimal treatment of neovascular age-related macular degeneration.

BACKGROUND New therapeutic approaches, particularly anti-vascular endothelial growth factor (anti-VEGF) therapies, prevent, and in some cases reverse, vision damage caused by age-related macular degeneration (AMD). Unequal access to care across Canada remains a problem for many retina specialists and their patients. OBJECTIVE To develop a consensus concerning the management of patients with exudative age-related macular degeneration (AMD). DESIGN Consensus document. PARTICIPANTS Ten Canadian retina specialists. METHODS The development of a consensus among Canadian experts concerning optimal treatment of AMD began with a review of the clinical evidence, daily practices, existing guidelines, and current national and international approvals and policies. The experts met on June 29, 2010, in Quebec City to discuss their findings and to propose strategies for consensus. RESULTS The result of this expert panel is a consensus proposal for Canadian ophthalmologists and retina specialists who are treating patients with or at risk for developing neovascular AMD. CONCLUSIONS The consensus provides guidelines to aid retina specialists in managing exudative AMD. Currently, ranibizumab is the only agent with sufficient Level I evidence and a Health Canada-approved indication for the treatment of wet AMD. Bevacizumab has been shown to be noninferior in preserving and improving visual acuity when compared to ranibizumab. Potential safety differences between the 2 drugs remain to be elucidated. The positioning of ranibizumab in this therapeutic area will be further defined as additional data for existing and emerging therapies become available. Until then, this agent remains the therapy of choice for individuals with neovascular AMD.

Management of pediatric choroidal neovascular membranes with intravitreal anti-VEGF agents: a retrospective consecutive case series

OBJECTIVE To report the results of pediatric choroidal neovascular membranes (CNVMs) secondary to a variety of etiologies treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents. DESIGN Retrospective case series. PARTICIPANTS Four pediatric patients at the Hosptial for Sick Children with CNVMs secondary to a variety of etiologies. METHODS Each patient received multiple treatments with one of the following anti-VEGF agents: pegaptanib sodium, bevacizumab, or ranibizumab. Progress was monitored by clinical exam, optical coherence tomography (OCT), and fluorescein angiography. RESULTS The mean age of our patients was 11.5 years (range, 8-15 years). Patients were followed for a mean of 10 months (range, 4-14 months). One patient was treated with pegaptanib sodium, 2 with bevacizumab, and 1 with ranibizumab. Following treatment, 1 patient showed an improvement and 3 showed stabilization of vision with reduction of fluid on clinical exam and OCT, and cessation of leakage on the fluorescein angiogram. Patients required 2-5 injections of the anti-VEGF agent. No ocular or systemic adverse events were observed in any of our treated patients. CONCLUSIONS Anti-VEGF agents were effective in the treatment of pediatric CNVMs in this case series. However, we do not know how these results would have differed from other treatment modalities, including observation. We did not observe any adverse side effects; however, larger studies are required to document the safety of these medications in the pediatric population where normal angiogenesis is occurring.