Stéphanie Baillif

Endophthalmitis After Intravitreal Injections: Incidence, Presentation, Management, and Visual Outcome

PURPOSE To report the incidence and characteristics of endophthalmitis after intravitreal injections of anti-vascular endothelial growth factor agents or corticosteroids and to describe the clinical and bacteriologic characteristics, management, and outcome of these eyes with acute endophthalmitis in France. DESIGN Retrospective, nationwide multicenter case series. METHODS From January 2, 2008 to June 30, 2013, a total of 316,576 intravitreal injections from 25 French ophthalmic centers were included. For each center, the number of intravitreal injections was determined using billing codes and the injection protocol was recorded. A registry and hospital records were reviewed to identify patients treated for endophthalmitis after injection during the same time period. The main outcome measures were the incidence of clinical endophthalmitis and visual acuity of endophthalmitis cases. RESULTS During the study period, 65 cases of presumed endophthalmitis were found, giving an overall incidence of 0.021% (2.1 in 10,000 injections) (95% confidence interval [CI], 0.016%-0.026%). The median number of days from injection to presentation was 4 [1-26] days. The most common symptom was vision loss. Bacterial identification was achieved in 43.4%. The most frequent pathogens were gram-positive bacteria (91.3%), including coagulase-negative Staphylococcus in 78.3%. Neither the interval between injection and presentation for endophthalmitis nor the clinical signs differentiated culture-positive from culture-negative cases. In multivariate analysis, the use of a disposable conjunctival mould assist device and the use of prophylaxis with an antibiotic or antiseptic were significantly associated with an increased incidence of endophthalmitis (P = .001). The majority of patients had worse visual acuity after 3 months of follow-up when compared with acuity before endophthalmitis. CONCLUSIONS The incidence of presumed endophthalmitis after intravitreal injections of anti-vascular endothelial growth factors or corticosteroids was low and the prognosis poor. Prevention and management remain challenging. It remains to be determined whether the findings of this study are relevant for other countries using different techniques for intravitreal injections.

Prognostic factors of liver metastases from uveal melanoma

ObjectivesThis study was designed to assess survival and identify prognostic factors for liver metastases diagnosed by systematic screening in uveal melanoma patients.MethodsAmong 602 consecutive patients treated over 10 years for uveal melanoma and followed by systematic semi-annual hepatic screening (abdominal ultrasonography), 63 (10.5%) developed liver metastases; these patients form the basis of this study. Factors including patient demographics, characteristics of the uveal tumor, metastasis-free interval, severity of liver metastatic involvement, and treatments of metastases were studied retrospectively regarding their prognostic value, using univariate (Kaplan-Meier method) and multivariate (Cox model) analyses.ResultsThirty-five patients (55.6% of the metastatic population) received systemic chemotherapy or best supportive care only; 14 patients (22.2% of the metastatic population) diagnosed with diffuse liver involvement had cytoreductive surgery and intra-arterial chemotherapy; 14 (22.2% of the metastatic population) had complete surgical removal of liver metastases followed by postoperative intra-arterial chemotherapy. No significant surgical complications were experienced. The median overall survival after diagnosis of liver metastases was 15 months. It reached 25 months for selected patients with complete resection (P=0.0002). In this cohort of 63 patients, ten or fewer preoperatively diagnosed metastases and primary uveal melanoma not involving the ciliary body were independently associated with better prognosis.ConclusionsThis study suggests that selected patients with screened liver metastases from uveal melanoma may benefit from aggressive treatment, including surgery. The two independent favorable prognostic factors are fewer than ten metastases at screening and the absence of ciliary body involvement.

Measurement of Subfoveal Choroidal Thickness After Cataract Surgery in Enhanced Depth Imaging Optical Coherence Tomography

PURPOSE To compare subfoveal choroidal thickness (SFCT) before and after uneventful cataract surgery using enhanced depth imaging optical coherence tomography (EDI-OCT). METHODS A prospective study was conducted on 115 eyes of 95 patients who had phacoemulsification. Measurements of SFCT were performed preoperatively, 1 day (D1), 7 days (D7), 1 month (M1), and 3 months (M3) after surgery using the EDI-OCT technique. Central retinal thickness (CRT) was measured before surgery and at M1 and M3. RESULTS The 95 patients had a mean age of 76 ± 8.3 years. The mean SFCT at baseline was 224 ± 75 μm. It showed a negative correlation with age and axial length (P = 0.03). The SFCT significantly increased after surgery with a mean value of 232 ± 76 μm at D1 (P < 0.001), 237 ± 78 μm at M1 (P < 0.001), and 232 ± 76 μm at M3 (P < 0.001). The mean CRT increased from 234 ± 48 μm at baseline to 248 ± 48 μm at M1 (P = 0.005), and 252 ± 81 μm at M3 (P = 0.001). Three (2.6%) patients developed a pseudophakic cystoid macular edema (PCME). The greatest progression of SFCT after phacoemulsification was observed for these patients. It preceded the occurrence of pseudophakic cystoid macular edema (PCME) by 1 month. CONCLUSIONS Mean SFCT increased after cataract surgery. The changes in baseline SFCT were greater in PCME patients and preceded the increase in CRT.

Adherence and kinetics of biofilm formation of Staphylococcus epidermidis to different types of intraocular lenses under dynamic flow conditions

PURPOSE: To compare the adherence and biofilm formation of Staphylococcus epidermidis under in vitro flow conditions on intraocular lenses (IOLs) made of 4 biomaterials: poly(methyl methacrylate) (PMMA), silicone, hydrophilic acrylic, and hydrophobic acrylic. SETTING: Department of Ophthalmology, Croix‐Rousse University Hospital and University Research Laboratory, Lyon, France. METHODS: Intraocular lenses were placed in a bioreactor designed to replicate intraocular conditions. The model consisted of Tygon tubing connected to a vial. Three septa allowed the entry and elimination of the artificial aqueous humor and inoculation of the bacterial suspension.The first of 2 pumps moved the aqueous humor along the circuit; the second pump regulated the flow at which the nutritive environment was regenerated. At various times (12, 16, 24, 40, 48, 60, and 72 hours), IOLs were taken from this environment and the bound bacteria were removed and counted. The distribution of bacterial adhesion on the IOLs was modeled using polynomial Poisson regression. To test the effect of the IOL biomaterial on bacterial adhesion, likelihood ratio tests were performed. RESULTS: The model provided the kinetics of S epidermidis biofilm growth on IOLs. The biofilm growth on each of the 4 biomaterials occurred in 3 phases: latent, dynamic or accelerated growth, and linear growth. The extent of bacterial binding to IOLs increased from hydrophilic acrylic polymer to PMMA, hydrophobic acrylic, and silicone. The differences were statistically significant. CONCLUSION: Bacterial adhesion to and biofilm development on the IOL surface depended on the characteristics of the biomaterial.

Effectiveness and safety of dexamethasone implants for postsurgical macular oedema including Irvine–Gass syndrome: the EPISODIC-2 study

Aim To assess the effectiveness and safety of intravitreal dexamethasone implants for treating post-surgical macular oedema, including Irvine-Gass syndrome refractory to first-line treatments. Methods Descriptive, observational, retrospective, consecutive, uncontrolled, multicentre, national case series. 50 patients were included in the study between March 2011 and June 2013 with a minimum 6 months follow-up. At baseline, each patient received a dexamethasone implant 0.7 mg (Ozurdex). Best-corrected visual acuity (BCVA), central subfield macular thickness (CSMT), and intraocular pressure (IOP) were measured at baseline and then monthly. The main outcome measure was the mean change in BCVA (in ETDRS letters (Early Treatment Diabetic Retinopathy Study): L) Results Baseline mean±SD BCVA was 55.7±15.4 L. At month 2, BCVA was 71.8±10.5 L and 61.2% of patients had an increase of more than 15 letters. Baseline mean CSMT was 544±117.2 μm and this decreased to 302 μm at month 2. Anatomic and functional recurrences were both first detected from month 3 and continued throughout follow-up, with values consistently above baseline. The peak in IOP was reached in month 1 with mean IOP of 15.3±4.6 mm Hg. Of the 39/50 patients followed up for 12 months, 49% received a second injection. The anatomic and functional response and safety patterns were similar to that obtained with the first intravitreal injection, demonstrating Ozurdex’s reproducibility. However, more than half of the patients followed-up for at least 1 year presented neither functional nor anatomical recurrence. Conclusions Ozurdex would appear to be an interesting alternative therapy for treating post-surgical macular oedema, including Irvine-Gass syndrome refractory to first-line treatments.

Local Recurrence After Uveal Melanoma Proton Beam Therapy: Recurrence Types and Prognostic Consequences

PURPOSE To study the prognosis of the different types of uveal melanoma recurrences treated by proton beam therapy (PBT). METHODS AND MATERIALS This retrospective study analyzed 61 cases of uveal melanoma local recurrences on a total of 1102 patients treated by PBT between June 1991 and December 2010. Survival rates have been determined by using Kaplan-Meier curves. Prognostic factors have been evaluated by using log-rank test or Cox model. RESULTS Our local recurrence rate was 6.1% at 5 years. These recurrences were divided into 25 patients with marginal recurrences, 18 global recurrences, 12 distant recurrences, and 6 extrascleral extensions. Five factors have been identified as statistically significant risk factors of local recurrence in the univariate analysis: large tumoral diameter, small tumoral volume, low ratio of tumoral volume over eyeball volume, iris root involvement, and safety margin inferior to 1 mm. In the local recurrence-free population, the overall survival rate was 68.7% at 10 years and the specific survival rate was 83.6% at 10 years. In the local recurrence population, the overall survival rate was 43.1% at 10 years and the specific survival rate was 55% at 10 years. The multivariate analysis of death risk factors has shown a better prognosis for marginal recurrences. CONCLUSION Survival rate of marginal recurrences is superior to that of the other recurrences. The type of recurrence is a clinical prognostic value to take into account. The influence of local recurrence retreatment by proton beam therapy should be evaluated by novel studies.

Long term follow-up after a single intravitreal ranibizumab injection for choroidal neovascularisation secondary to optic nerve head drusen in a 5-year-old child

Dear Editor, A 5-year-old boy presented with a 10-day history of blurred vision in his left eye. Visual acuity (VA) was 20/60. Funduscopy, ultrasonography, and Fluorescein/ICG angiographies (Fig. 1) associated with optical coherence tomography (OCT) (Fig. 2a,b) revealed a classic choroidal neovascular (CNV) membrane complicating buried optic nerve head drusen (ONHD). After an informed consent was obtained, the patient underwent an intravitreal ranibizumab injection (0.5 mg) under general anaesthesia. VA improved to 20/30 at month 1, 20/25 at month 2 and remained stable over a 12month follow-up period. No recurrence of the neovascular activity was observed (Fig. 2c,d). CNV is a rare complication of ONHD in children [1]. It has been treated with macular surgery [2, 3], laser photocoagulation [4], and photodynamic therapy [5]. Recently anti-VEGF agents have successfully been used in combination [6] or as a monotherapy [7, 8]. Thus, an 11-yearold boy underwent 3 systematic monthly ranibizumab injections over 6 months of follow-up [8]. A 12-year-old girl received two injections of ranibizumab performed as required (PRN) over a 12-months period [7]. Our patient was successfully treated with a single ranibizumab injection. CNV secondary to ONHD seems to be sensitive to anti-VEGF agents. In these cases, a PRN regimen should be recommended. This case has been partly presented at the French Society of Ophthalmology Meeting in May 2012, Paris, France. S. Baillif : E. Nguyen Centre Hospitalier, Universitaire Saint Roch, Nice, France

Kératoglobe : revue de la littérature

Le keratoglobe est une affection corneenne non inflammatoire, bilaterale, rare, caracterisee par une protrusion de l’ensemble de la cornee associee a un amincissement diffus plus prononce en peripherie. Le keratoglobe est le plus souvent congenital, mais des formes acquises sont decrites. La deformation corneenne est responsable d’une gene visuelle majeure puisqu’elle induit une myopisation importante, un astigmatisme irregulier et des opacites corneennes sequellaires en cas d’hydrops aigu. La correction optique par lunettes est indiquee tant qu’elle permet une acuite visuelle utile. La prise en charge chirurgicale des keratoglobes reste difficile du fait de l’extreme finesse corneenne. La keratoplastie transfixiante fut l’une des premieres techniques proposees, mais elle est en partie delaissee en faveur de procedures chirurgicales souvent multiples et beaucoup plus complexes.

Implant intraoculaire et adhésion bactérienne : influence des conditions environnementales, des propriétés bactériennes et des caractéristiques du biomatériau

Adhesion of bacteria to intraocular lenses is an important step in the pathogenesis of postoperative endophthalmitis. It can be described as a two-phase process including an initial, instantaneous, and reversible phase followed by a time-dependant and irreversible molecular and cellular phase. The binding of bacteria is affected by many factors including environmental factors such as medium composition, presence of proteins and flow conditions, the bacterial cell surface characteristics, and the materials surface properties. This article reviews all these factors affecting the adhesion of bacteria to intraocular lenses. A better understanding of these mechanisms would make it possible to reduce the bacterial adhesion process and thus could help decrease the incidence of postoperative endophthalmitis.

Biofilms à Staphylococcus epidermidis à la surface des implants intraoculaires

Bacterial adhesion to intraocular lenses (IOLs) takes place during their implantation. This is a prominent etiological factor of postoperative endophthalmitis. Following adhesion, secretion of an extracellular matrix (called slime for Staphylococcus epidermidis) and formation of multiple layers of microcolonies lead to the colonization of the biomaterial surface. Scanning electron microscopy photographs illustrate the different steps of biofilm formation. The different adhesins expressed by S. epidermidis involved in the adhesion process are described. The biofilm is not only an adhesive medium; it also affects virulence. Last, notions on biofilm physiology are discussed in an attempt to explain the dynamic equilibrium of this system. In 2004, the perfect biomaterial able to prevent postoperative endophthalmitis does not yet exist. Moreover, there is no effective tool, at the present time, to fight against mature biofilms. Therefore, preventing biofilm formation remains capital, which requires perfect knowledge of all stages of formation and the factors involved.