C. Creuzot-Garcher

Differences in meibomian fatty acid composition in patients with meibomian gland dysfunction and aqueous-deficient dry eye

Aims: To evaluate the differences in meibomian fatty acid composition in healthy subjects and in patients suffering from meibomian gland dysfunction or aqueous-deficient dry eye. Methods: We collected meibomian oil using a sterile Schirmer paper in healthy individuals (nu200a=u200a20), dry eye patients (aqueous-deficient) (nu200a=u200a32) and meibomian gland dysfunction (MGD) patients (nu200a=u200a25) after gentle massage of the lid margin. Meibomian fatty acids were directly transmethylated and analysed using gas chromatography (GC) and GC mass spectrometry. Results: Meibomian fatty acids were similar in healthy individuals and in dry eye patients but were different in MGD patients, who showed significantly higher levels of branched-chain fatty acids (29.8% vs 20.2%) (p<0.0001) and lower levels of saturated fatty acids (9.3 vs 24.6%) (p<0.0001), in particular lower levels of palmitic (C16) and stearic (C18) acids. Conclusion: The increase in branched-chain fatty acids may reflect greater quantities of wax and cholesterol esters and triglycerides in meibomian gland excreta. Since wax and cholesterol esters are the main lipids of meibum, these differences may have physical consequences for tear-film lipid-layer fluidity and stability. Meibomian fatty acid composition and particularly the increase in branched chains could be a marker for meibomian gland dysfunction.

Intravitreal Aflibercept for Macular Edema Secondary to Central Retinal Vein Occlusion: 18-Month Results of the Phase 3 GALILEO Study

PURPOSEnTo evaluate intravitreal aflibercept for treatment of macular edema secondary to central retinal vein occlusion (CRVO).nnnDESIGNnRandomized, double-masked, phase 3 study.nnnMETHODSnA total of 177 patients with macular edema secondary to CRVO were randomized to receive 2 mg intravitreal aflibercept (n = 106) or sham (n = 71) every 4 weeks for 20 weeks. From weeks 24 to 48, patients were monitored every 4 weeks; the former group received intravitreal aflibercept as needed (PRN), and the sham group received sham. From weeks 52 to 76, patients were monitored every 8 weeks, and both groups received intravitreal aflibercept PRN. The primary endpoint (proportion of patients who gained ≥15 letters) was at week 24. This study reports exploratory outcomes at week 76.nnnRESULTSnThe proportion of patients who gained ≥15 letters in the intravitreal aflibercept and sham groups was 60.2% vs 22.1% at week 24 (patients discontinued before week 24 were considered nonresponders; P < .0001), 60.2% vs 32.4% at week 52 (last observation carried forward, P < .001), and 57.3% vs 29.4% at week 76 (last observation carried forward; P < .001). Mean μm change from baseline central retinal thickness was -448.6 vs -169.3 at week 24 (P < .0001), -423.5 vs -219.3 at week 52 (P < .0001), and -389.4 vs -306.4 at week 76 (P = .1122). Over 76 weeks, the most common ocular serious adverse event in the intravitreal aflibercept group was macular edema (3.8%).nnnCONCLUSIONSnThe visual and anatomic improvements seen after fixed, monthly dosing at week 24 were largely maintained when treatment intervals were extended. Patients with macular edema following CRVO benefited from early treatment with intravitreal aflibercept.

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

PURPOSEnTo 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.nnnDESIGNnRetrospective, nationwide multicenter case series.nnnMETHODSnFrom 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.nnnRESULTSnDuring 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.nnnCONCLUSIONSnThe 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.

Dominant variants in the splicing factor PUF60 cause a recognizable syndrome with intellectual disability, heart defects and short stature

Verheij syndrome, also called 8q24.3 microdeletion syndrome, is a rare condition characterized by ante- and postnatal growth retardation, microcephaly, vertebral anomalies, joint laxity/dislocation, developmental delay (DD), cardiac and renal defects and dysmorphic features. Recently, PUF60 (Poly-U Binding Splicing Factor 60u2009kDa), which encodes a component of the spliceosome, has been discussed as the best candidate gene for the Verheij syndrome phenotype, regarding the cardiac and short stature phenotype. To date, only one patient has been reported with a de novo variant in PUF60 that probably affects function (c.505C>T leading to p.(His169Tyr)) associated with DD, microcephaly, craniofacial and cardiac defects. Additional patients were required to confirm the pathogenesis of this association and further delineate the clinical spectrum. Here we report five patients with de novo heterozygous variants in PUF60 identified using whole exome sequencing. Variants included a splice-site variant (c.24+1G>C), a frameshift variant (p.(Ile136Thrfs*31)), two nonsense variants (p.(Arg448*) and p.(Lys301*)) and a missense change (p.(Val483Ala)). All six patients with a PUF60 variant (the five patients of the present study and the unique reported patient) have the same core facial gestalt as 8q24.3 microdeletions patients, associated with DD. Other findings include feeding difficulties (3/6), cardiac defects (5/6), short stature (5/6), joint laxity and/or dislocation (5/6), vertebral anomalies (3/6), bilateral microphthalmia and irido–retinal coloboma (1/6), bilateral optic nerve hypoplasia (2/6), renal anomalies (2/6) and branchial arch defects (2/6). These results confirm that PUF60 is a major driver for the developmental, craniofacial, skeletal and cardiac phenotypes associated with the 8q24.3 microdeletion.

Methanol poisoning: two case studies of blindness in Indonesia.

We report two recent cases of methanol intoxication in French patients living in Bali. These intoxications were secondary to the consumption of adulterated liquor. Both patients presented acute bilateral loss of vision a few days after methanol ingestion with no sign of recovery. The fundus showed bilateral optic atrophy that was well correlated with retinal nerve fibre layer thickness measured with spectral-domain optical coherence tomography and compatible with toxic optic neuropathy. In one of the patients, macular swelling in one eye was observed. Electroretinograms were normal contrasting with abolished visual evoked potentials. Methanol was isolated from a sample of the beverage with gas chromatography. Methanol intoxication may occur in Asia and therefore adequate information for tourists and the local population is required.

Cholesterol metabolism and glaucoma: Modulation of Muller cell membrane organization by 24S-hydroxycholesterol

Glaucoma is a progressive and irreversible blinding neuropathy that is characterized by the loss of retinal ganglion cells (RGCs). Muller Glial Cell (MGC) activation is induced in retinal gliosis. MGCs are the most numerous glial cells in the retina and one of their roles is to sustain cholesterol homeostasis. 24S-hydroxycholesterol (24S-OHC) is one of the form of cholesterol elimination from the retina and is overexpressed during glaucoma. The objective of this study was to determine whether 24S-OHC triggers MGC membrane dynamics involving lipid rafts and contributes to gliosis at early and late time points. A proteomic analysis was carried out by nanoLC-MS/MS in raft and non-raft fractions from MGCs after treatment with 24S-OHC (10μM). The expression of structural and functional proteins was further analyzed by Western-blotting, as well as the levels of GM3 ganglioside by LC-MS. Cholesterol, sphingomyelin, saturated fatty acids and ganglioside GM3 are enriched in the rafts fractions in MGCs. Caveolin-1, flotillin-1, connexin-30 and -43 are localized in the MGCs rafts. Proteins implicated in adhesion or oxidative stress pathways in raft fractions were up and down-regulated by the treatment. Our data showed that 24S-OHC induced early changes in protein distribution in raft microdomains; however, further studies are needed to better characterize the surrounded mechanisms.

Étude préliminaire sur l’efficacité de trois injections intravitréennes de bevacizumab dans le traitement de la dégénérescence maculaire liée à l’âge exsudative

INTRODUCTIONnTo evaluate intravitreal bevacizumab therapy for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).nnnMATERIAL AND METHODSnA retrospective review between June 2006 and May 2008 of patients with CNV secondary to AMD was conducted. All patients were treated with intravitreal injection of bevacizumab (1.25mg) once a month during a 3-month-period. The mean evaluation criteria were the best-corrected visual acuity (BCVA) logMar testing before and one month after the third injection. All eyes underwent an angiography and an optical coherence tomography before injections to define the activity and the type of CNV and then to evaluate the persistence of leakage (macular edema, subretinal fluid, and pigment epithelial detachment) after treatment. Then treatments were left to the investigators discretion during the following six months.nnnRESULTSnSeventy-one eyes of 66 patients were enrolled. There were 65% occult CNV, 20% classic CNV, and 15% combined. A significant improvement in BCVA was observed, from 0.88±0.57 to 0.77±0.60 (p=0.001), one month after the third injection. At this time, 57.7% of the eyes required a reinjection because of leakage persistence. A concomitant treatment with intravitreal triamcinolone injection and/or photodynamic therapy was necessary for 8% of nonresponder eyes. Six months after initial treatment, a complete resolution of exudative signs was not obtained for 33.8% of eyes. The average number of injections was 3.85±0.96 during the 9-month follow-up. BCVA stability was observed at 4, 6 and 9-month follow-ups (F(71.2)=1.54; p=0.46). Three complications occurred: one endophthalmitis, one retinal tear, and one vitreous hemorrhage secondary to a macular hemorrhage.nnnDISCUSSIONnMean BCVA significantly improved at one month after three consecutive monthly intravitreal injections of bevacizumab. However, most eyes required a reinjection.nnnCONCLUSIONnIn spite of improvement in BCVA, leakage of the CNV persisted in most eyes after three monthly intravitreal injections of bevacizumab. Then retreatment and sometimes concomitant treatment was necessary to obtain complete resolution of exudative signs and BCVA stability.

Trends in operating room-based glaucoma procedures in France from 2005 to 2014: a nationwide study

Purpose To report the trends in operating room-based glaucoma procedures from 2005 to 2014 in France. Methods We identified operating room-based glaucoma procedures (trabeculectomies, deep sclerectomies, aqueous shunts and ciliary body destructions) performed in France from 2005 to 2014 by means of billing codes from a national database. The annual rates and incidence of these procedures per 100u2005000 inhabitants were analysed globally and in three age groups: 0–14u2005years, 15–59u2005years and over 60u2005years. Results The annual rate of trabeculectomies decreased slightly during the study period, while the rate for other surgical techniques (deep sclerectomies, aqueous drainage procedures and ciliary body destructions) increased. The overall rate of glaucoma surgeries was higher in areas with populations of African descent than in areas predominantly composed of Caucasian populations: 1.60 (95% CI 1.51 to 1.70, p<0.0001). Conclusions Trabeculectomy was the most commonly performed operating room-based glaucoma procedure in France from 2005 to 2014. Other modalities such as deep sclerectomies, aqueous drainage procedures and ciliary body destruction gained greater acceptance among French ophthalmologists during this 10-year period.

Early versus delayed intravitreal betamethasone as an adjuvant in the treatment of presumed postoperative endophthalmitis: a randomised trial

Aim To compare early versus delayed intravitreal betamethasone as an adjuvant in the treatment of presumed acute postoperative endophthalmitis after phacoemulsification. Methods Patients with presumed postcataract surgery endophthalmitis were included in this prospective, randomised, multicentre study. On admission, patients received intravitreal vancomycin and ceftazidime, and were randomly assigned to intravitreal betamethasone injection (early-IVB) group or no immediate injection (delayed-IVB) group. After 48u2005h, a second intravitreal antibiotic injection associated with intravitreal betamethasone was given to all patients. In patients with severe endophthalmitis or clinical deterioration, a prompt or delayed vitrectomy was performed. The primary outcome was the proportion of patients achieving a visual acuity (VA) of 20/40 or better at 12u2005months. The secondary outcomes were the rate of delayed vitrectomy and the rate of complications (retinal detachment and phthisis). Results Ninety-seven eyes of 97 patients were included, 45 in the early-IVB group and 52 in the delayed-IVB group. Overall, 62.9% of patients achieved a VA ≥20/40 at 1u2005year. There was no statistically significant difference in the visual outcome between the two groups at 1u2005year, whatever their baseline VA or light perception or hand motion or more (p=0.55 and p=0.10, respectively). The rates of delayed vitrectomy, retinal detachment and phthisis bulbi were not significantly different between the two groups (p=0.42, p=0.37 and p=0.44, respectively). Conclusions Early intravitreal betamethasone had no clear advantage versus delayed injection in the management of presumed postoperative endophthalmitis.

Métastase irienne révélatrice d’un cancer bronchopulmonaire

We report the case of a 53-year-old patient referred by his ophthalmologist for a red, painful eye. On exam, he demonstrated findings of granulomatous uveitis with ocular hypertension (38 mm Hg) and a whitish, vascularized iris tumor with invasion of the irido-corneal angle. As our first hypothesis was an iris metastasis, a systemic work-up was carried out, which revealed moderately differentiated broncho-pulmonary carcinoma with multiple metastases (brain, cerebellum and adrenal). Emergency radio-chemotherapy was initiated, and the outcome was good, with rapid regression of the iris metastasis and good efficacy against the primary cancer. After one year of follow-up, the patient developed a metastasis at a new site, and his general condition deteriorated.