Richard S. Kaiser

Acute endophthalmitis following intravitreal triamcinolone acetonide injection

Abstract Purpose To report the clinical features, causative organisms, management, and visual acuity outcomes of eight eyes of eight patients who developed acute postoperative endophthalmitis following intravitreal injection of triamcinolone acetonide (IVTA). Design Retrospective, multicenter, interventional, case series. Methods A retrospective, interventional, case series of all patients with acute postoperative endophthalmitis following IVTA at seven academic clinical centers between March 2001 and July 2002. Results A total of 922 IVTAs were performed. Eight eyes of eight patients with acute postoperative endophthalmitis were identified in the 6 weeks following IVTA for an incidence of 0.87% (95% confidence interval of 0.38% to 1.70%). The median time to presentation was 7.5 days (range, 1–15 days) after IVTA. The most common clinical findings were iritis (n = 8), vitritis (n = 8), hypopyon (n = 8), pain (n = 7), red eye (n = 6), and decreased vision (n = 5). The median presenting visual acuity was 20/1127 (range, 20/60 to light perception). Initial treatment consisted of vitreous tap and injection of antibiotics (n = 6) or pars plana vitrectomy and injection of intravitreal antibiotics (n = 2). Intraocular cultures yielded identification in seven patients. One demonstrated intracellular gram-positive cocci in chains with numerous polymorphonuclear cells on gram stain. The median postinfection vision was 20/400 (range, 20/40 to no light perception). Three patients ended up with no light perception visual acuity, including enucleation (n = 1) and phthisis (n = 1). Conclusions Acute postoperative endophthalmitis following IVTA occurs rapidly and can result in severe loss of vision.

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.

Intravitreal bevacizumab (avastin) in central retinal vein occlusion.

Purpose: To describe the effects of intravitreal bevacizumab in eyes with macular edema resulting from central retinal vein occlusions (CRVO). Methods: Retrospective consecutive case series of patients diagnosed with macular edema from CRVO who received intravitreal bevacizumab. Results: Thirty eyes of 29 patients with an average age of 72 years (range, 54–87 years) had intravitreal bevacizumab injections. Mean follow-up was 18.1 weeks. Initial mean visual acuity was 20/394. At the 1- and 2-month follow-up, mean visual acuity improved to 20/237 (n = 26, P = 0.04) and 20/187 (n = 21, P = 0.008), respectively. At the 3- and 4-month follow-up, visual acuity improved from 20/228 to 20/157 (n = 15, P = 0.05) and from 20/313 to 20/213 (n = 11, P = 0.03), respectively. No significant changes in visual acuity were found after 4 months though the number of patients in this group was small. Duration of treatment effect following an injection appears to be limited to 2 months for most patients. No ocular or systemic adverse reactions were noted. Conclusions: The visual benefits of intravitreal bevacizumab for macular edema due to CRVO are apparent early but are not sustained without repeated injections. Larger clinical studies with long-term follow-up will be necessary to better elicit the best regimen for this therapy.

Intravitreal bevacizumab for refractory pigment epithelial detachment with occult choroidal neovascularization in age-related macular degeneration.

Purpose: New medications targeting vascular endothelial growth factor show promise in the treatment of wet macular degeneration. This study describes the clinical response and optical coherence tomography (OCT) findings for patients with refractory pigment epithelial detachment (PED) and occult choroidal neovascular membranes (CNVMs) who were treated with intravitreal bevacizumab. Methods: A retrospective analysis of data for 10 patients with fibrovascular PEDs, initially treated with intravitreal pegaptanib, thermal laser, or photodynamic therapy with or without triamcinolone acetonide administration, was performed. All patients were refractory to previous treatment. They received monthly injections of bevacizumab and were followed by clinical examination, angiography, and OCT. Results: Nine of 10 patients had stable or improved vision. Angiogram findings showed resolution of leakage from CNVMs. OCT demonstrated resolution of the subretinal or intraretinal fluid but persistence of the PED itself. Vision improvement was correlated with OCT changes. Conclusion: Intravitreal bevacizumab may be a viable option in treating patients with fibrovascular PEDs. OCT findings suggest that visual improvement is secondary to resolution of subretinal and intraretinal edema without resolution of the PED.

Bevacizumab for Neovascular Age-Related Macular Degeneration Using a Treat-and-Extend Regimen: Clinical and Economic Impact

PURPOSE To evaluate the visual outcomes, number of injections, and direct medical cost of a treat-and-extend regimen in managing neovascular age-related macular degeneration with intravitreal bevacizumab. DESIGN Retrospective, interventional, consecutive case series. METHODS Seventy-four eyes of 73 patients with treatment-naïve neovascular age-related macular degeneration from a single clinical practice were treated monthly with intravitreal bevacizumab until no intraretinal or subretinal fluid was observed on optical coherence tomography. The treatment intervals then were lengthened sequentially by 2 weeks until signs of exudation recurred and then were reduced accordingly to maintain an exudation-free macula. Main outcomes measured included mean change from baseline visual acuity, proportion of eyes losing fewer than 3 and gaining 3 or more Snellen visual acuity lines at 1 year of follow-up, annual mean number of injections, optical coherence tomography mean central retinal thickness change from baseline, mean maximum period of extension, adverse events, and mean direct annual medical cost. RESULTS The mean follow-up period was 1.41 years. Mean Snellen visual acuity improved from 20/230 at baseline to 20/109 at 12 months (P < .001) and 20/106 at 24 months (P < .001). The mean number of injections over the first year was 7.94. The mean optical coherence tomography central retinal thickness decreased from 316 to 239 μm at 12 months (P < .001). The mean direct medical cost over the first year was

Adult retinopathy of prematurity: Outcomes of rhegmatogenous retinal detachments and retinal tears

3493.85. CONCLUSIONS Eyes with neovascular age-related macular degeneration experienced significant visual improvements on average when managed with intravitreal bevacizumab using a treat-and-extend regimen with fewer patient visits and injections along with lower costs compared with a fixed, monthly dosing regimen.

Association between high-risk disease loci and response to anti-vascular endothelial growth factor treatment for wet age-related macular degeneration.

PURPOSE To describe the results of retinal tears and rhegmatogenous retinal detachments (RD) in adults with retinopathy of prematurity (ROP). DESIGN Noncomparitive interventional case series. METHODS Retrospective cohort of 216 eyes of 108 patients, 15 years or older, followed for up to 23 years (median, 6.2 years). RESULTS One eye was initially seen with an RD, and during follow-up 30 eyes had an RD develop. An additional surgical procedure was required in 7 of the 31 eyes (23%) with an RD. Four eyes were initially seen with retinal tears, and during follow-up 19 eyes had a retinal tear develop. Seven of the 23 eyes (30%) with a retinal tear had initial repair fail. Eyes with minimal cicatricial changes from ROP were still at high risk for tears and detachments developing. Eighty percent of eyes with retinal tears and 60% of eyes with an RD that started with vision >20/60 maintained that level of vision at the final examination. CONCLUSION In patients with a history of premature birth, features of fundus examinations do not correlate with the occurrence of a retinal tear or RD. Repair of a tear or detachment in such a patient is more likely to require multiple procedures but can still be associated with good visual results. Physicians should consider widespread relief of vitreoretinal traction for a tear or detachment in any patient with a history of premature birth.

Variability in fluorescein angiography interpretation for photodynamic therapy in age-related macular degeneration.

Purpose: To investigate whether there is an association between known age-related macular degeneration genetic risk variants in the CFH, ARMS2, and HTRA1 genes and response to anti–vascular endothelial growth factor (VEGF) (ranibizumab or bevacizumab) treatment for wet age-related macular degeneration. Methods: A retrospective review of 150 patients with documented wet age-related macular degeneration based on clinical examination and fluorescein angiogram was performed. Patients received anti-VEGF therapy with ranibizumab and/or bevacizumab. Patients were genotyped for the single-nucleotide polymorphism rs1061170, rs10490924, rs3750848, rs3793917, rs11200638, and rs932275 and for the indel del443ins54 spanning the CFH, ARMS2, and HTRA1 genes. Results: There were 57 patients who were characterized as negative responders to anti-VEGF therapy, and 93 patients who were characterized as positive responders. There was no significant difference in mean baseline visual acuity between the groups. Negative responders were followed for a mean duration of 24.0 months, while positive responders were followed for a mean duration of 22.0 months. Although the frequency of the at-risk alleles was higher in the positive responders when compared with the negative responder, this did not reach statistical significance. Additionally, there was no significant association between genotype and the number of injections or absolute change in visual acuity in both groups of responders. Conclusion: In our patient cohort, there was no statistically significant association between response to anti-VEGF therapy and the genotype in both positive-responder and negative-responder groups. Larger studies with more power are necessary to further determine whether a pharmacogenetic association exists between wet age-related macular degeneration and anti-VEGF therapy.

Clinical management of proliferative vitreoretinopathy: an update.

Objectives To investigate the variability in fluorescein angiography interpretation for photodynamic therapy in age-related macular degeneration. Methods Eight graders, who included two TAP-certified ophthalmologists, three other retinal specialists, two fellows in vitreoretinal diseases, and a senior fundus photograph grader, evaluated fluorescein angiograms of six patients treated according to the Treatment for ARMD With Verteporfin (TAP) protocol at a single center. Each patient’s baseline angiogram was evaluated to determine whether the CNV lesion was predominantly (≥50%) classic. For each follow-up angiogram, at 3, 6, 12, and 24 months, the grader was required to determine whether fluorescein leakage was present. Six months after the initial gradings, each reader was again presented with the baseline angiogram for each patient and once again asked to determine whether the CNV lesion was predominantly classic without knowledge of the previous grading. All gradings were performed without knowledge of the clinical course. Results In grading initial visit and follow-up visit angiograms, the overall concordance rates were 81% and 82%, respectively. Concordance rates were not statistically different between the group as a whole when compared with the gradings of the two TAP-certified ophthalmologists. When initial visit angiograms were regraded, an intraobserver variability of 17% was noted. Overall, gradings were discordant with the majority opinion in approximately 19% of decisions. Conclusions Considerable variability can be expected in fluorescein angiography interpretation as the results of the TAP investigation are applied to clinical practice.

Pars plana vitrectomy and scleral buckle versus pars plana vitrectomy alone for patients with rhegmatogenous retinal detachment at high risk for proliferative vitreoretinopathy.

Background: Proliferative vitreoretinopathy (PVR) remains the most significant obstacle to successful retinal reattachment surgery. Preclinical studies continue to add insights into the complex molecular events leading to PVR development, helping to identify new targets for potential prophylactic or therapeutic agents. This article reviews the recent evidence supporting surgical and medical treatments for PVR. Methods: PUBMED was used for literature search. Clinical studies regarding surgical management of PVR from January 1, 2000 to August 1, 2014 were included. Clinical studies regarding medical management of PVR from January 1, 2000 to August 1, 2014 were included if the design of study was a randomized controlled trial. Results: Many recent studies have evaluated surgical and medical strategies for the treatment and prevention of PVR. Newer vitreoretinal surgery technology (23- and 25-gauge vitrectomy) and tamponade agents (heavy silicone oils) have been studied. Medical therapies evaluated include antiinflammatory agents, low molecular weight heparin, 5-fluorouracil, 13-cis-retinoic acid, and daunorubicin, amongst others. Conclusion: Surgical management with pars plana vitrectomy, with or without scleral buckle or inferior retinectomy, remains an effective treatment for PVR-related detachments. Consensus regarding a preferred surgical strategy remains controversial. Many medical therapies have been studied but fail to demonstrate a statistically significant benefit in clinical trials. Further studies to clarify the efficacy of available and novel treatment options are warranted.