Christophe Chiquet

Non‐arteritic anterior ischaemic optic neuropathy is nearly systematically associated with obstructive sleep apnoea

Aim: To evaluate newly diagnosed non-arteritic anterior ischaemic optic neuropathy (NAION) patients for the existence of an associated sleep apnoea syndrome. Methods: Newly identified NAION patient underwent polysomnography. The prevalence of sleep apnoea in NAION patients was compared to the prevalence previously found in the general population. Hypertension, diabetes, hyperlipidaemia, and atheromatous lesions of carotid vessels as classic risk factors associated with NAION were also identified. Results: 27 consecutive newly diagnosed NAION patients (18 men and nine women, mean age 65 (SD 8) years, body mass index 27.2 (3.8) kg/m2) were included in the study. 24 of these 27 NAION patients (89%) exhibited a sleep apnoea syndrome (respiratory disturbance index: 37.2/h (SD 18.3/h). Risk ratio for a NAION patient to have sleep apnoea was 4.9 compared to the general population (p<0.001). Sleep apnoea was 1.5–2-fold more frequent than the rate of the other identified risk factors typically associated with NAION (hypertension, diabetes). Conclusions: Sleep apnoea is the most frequent disorder associated with NAION and should be screened in this population. At least a questionnaire related to obstructive sleep apnoea symptoms and assessment of sleepiness should be systematically proposed to patients with NAION.

Eubacterial PCR for bacterial detection and identification in 100 acute postcataract surgery endophthalmitis.

PURPOSE To evaluate eubacterial PCR compared with conventional cultures for detection and identification of bacterial agents in ocular samples from patients with acute postcataract endophthalmitis. METHODS Broad-range eubacterial PCR amplification was used, followed by direct DNA sequencing in ocular samples (aqueous humor, vitreous samples from tap or vitrectomy) from 100 consecutive patients presenting with acute postcataract endophthalmitis. Bacterial cultures were performed on the same ocular samples by using traditional methods (brain-heart infusion broth). RESULTS At the time of admission, the detection rate was not significantly different between cultures and PCR (38.2% for cultures versus 34.6% for PCR in aqueous humor samples; 54% versus 57% in vitreous from a vitreous tap). In contrast, in the vitreous obtained from vitrectomy, after intravitreous injection of antibiotics, PCR detected bacteria in 70% of the cases, compared with 9% in cultures. By combining PCR and cultures, bacterial identification was obtained in 47% of aqueous humor samples at admission, in 68% of vitreous samples from a vitreous tap at admission, and in 72% of vitreous samples from pars plana vitrectomy. Gram-positive bacteria predominated (94.3%). The concordance between cultures and PCR was 100%. The contamination rate was 2%. CONCLUSIONS Cultures and eubacterial PCR are complementary techniques for bacterial identification in eyes with acute postcataract endophthalmitis. PCR technique was needed for identification of the involved microbial pathogen in 25% of all the cases. Eubacterial PCR is more effective than cultures in detecting bacteria in vitreous samples from patients with previous intravitreous administration of antibiotics.

Structure-function relationships with spectral-domain optical coherence tomography retinal nerve fiber layer and optic nerve head measurements.

PURPOSE To evaluate the regional structure-function relationship between visual field sensitivity and retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) measurements using spectral-domain optical coherence tomography (SD-OCT). METHODS Prospective cross-sectional study conducted on patients with glaucoma, suspected glaucoma, and healthy subjects. Eyes were tested on Cirrus OCT and standard achromatic perimetry. RNFL thickness of 12 peripapillary 30° sectors, neuroretinal rim thickness extracted from 36 neuroretinal rim scans, and Bruch membrane opening minimum rim width (BMO-MRW)-a recently defined parameter-extracted from 36 neuroretinal rim scans were obtained. Correlations between peripapillary RNFL thickness, neuroretinal rim thickness, all six sectors of BMO-MRW, and visual field sensitivity in the six corresponding areas were evaluated using logarithmic regression analysis. Receiver operating curve areas were calculated for each RNFL, ONH, and macular ganglion cell analysis parameter. RESULTS We included 142 eyes of 142 subjects. The correlations (r(2)) between RNFL thickness, Cirrus-based neuroretinal rim thickness, BMO-MRW and visual field sensitivity ranged from 0.07 to 0.60, 0.15 to 0.49, and 0.24 to 0.66, respectively. The structure-function correlations were stronger with BMO-MRW than with Cirrus-based neuroretinal rim thickness. The largest areas under the receiver operating curve were seen for rim area (0.926 [95% confidence interval 0.875, 0.977]; P < 0.001) in eyes with glaucoma and for average RNFL (0.863 [0.769, 0.957]; P < 0.01) in eyes with suspected glaucoma. CONCLUSIONS The structure-function relationship was significantly stronger with BMO-MRW than other ONH SD-OCT parameters. The best diagnostic capabilities were seen with rim area and average RNFL.

24-Hour Intraocular Pressure Rhythm in Young Healthy Subjects Evaluated With Continuous Monitoring Using a Contact Lens Sensor

IMPORTANCE This study evaluates a new device that has been proposed to continuously monitor intraocular pressure (IOP) over 24 hours. OBJECTIVE To evaluate 24-hour IOP rhythm reproducibility during repeated continuous 24-hour IOP monitoring with noncontact tonometry (NCT) and a contact lens sensor (CLS) in healthy participants. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study of 12 young healthy volunteers at a referral center of chronobiology. INTERVENTIONS Participants were housed in a sleep laboratory and underwent four 24-hour sessions of IOP measurements over a 6-month period. After initial randomized attribution, the IOP of the first eye was continuously monitored using a CLS and the IOP of the fellow eye was measured hourly using NCT. Two sessions with NCT measurements in 1 eye and CLS measurements in the fellow eye, 1 session with CLS measurements in only 1 eye, and 1 session with NCT measurements in both eyes were performed. MAIN OUTCOMES AND MEASURES A nonlinear least squares, dual-harmonic regression analysis was used to model the 24-hour IOP rhythm. Comparison of acrophase, bathyphase, amplitude, midline estimating statistic of rhythm, IOP values, IOP changes, and agreement were evaluated in the 3 tonometry methods. RESULTS A significant nyctohemeral IOP rhythm was found in 31 of 36 sessions (86%) using NCT and in all sessions (100%) using CLS. Hourly awakening during NCT IOP measurements did not significantly change the mean phases of the 24-hour IOP pattern evaluated using CLS in the contralateral eye. Throughout the sessions, intraclass correlation coefficients of the CLS acrophase (0.6 [95% CI, 0.0 to 0.9]; P = .03), CLS bathyphase (0.7 [95% CI, 0.1 to 0.9]; P = .01), NCT amplitude (0.7 [95% CI, 0.1 to 0.9]; P = .01), and NCT midline estimating statistic of rhythm (0.9 [95% CI, 0.9 to 1.0]; P < .01) were significant. When performing NCT measurements in 1 eye and CLS measurements in the contralateral eye, the IOP change at each point normalized from the first measurement (9 am) was not symmetric individually or within the population. CONCLUSIONS AND RELEVANCE The CLS is an accurate and reproducible method to characterize the nyctohemeral IOP rhythm in healthy participants but does not allow for estimating the IOP value in millimeters of mercury corresponding to the relative variation of the electrical signal measured.

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.

Value of two mortality assessment techniques for organ cultured corneal endothelium: trypan blue versus TUNEL technique

Background/aim: It is known that trypan blue staining is not a good predictor of loss of corneal endothelial cells (ECs) during organ culture. As it is primarily an indicator of membrane integrity, it would also not be expected to identify ECs undergoing apoptosis. The aim of this study was to determine the ability of the in situ TdT dUTP mediated nick end labelling (TUNEL) technique to detect cell death in the corneal endothelium caused by apoptosis during organ culture, compared with conventional vital staining with trypan blue. Methods: 31 human corneas were organ cultured at 31°C for 3–35 days. Staurosporine was used to induce apoptosis in five control corneas. The endothelium was assessed by trypan blue and by the in situ TUNEL technique. The percentages of trypan and TUNEL positive ECs were compared. Their links with sex, donor age, time from donor death and organ culture, initial and final EC density and cell loss were studied. Results: TUNEL stained ECs were observed in all corneas. TUNEL positive ECs were mostly located either in corneal folds or at the periphery of corneal folds showing central shedding. The mean percentage of cell death at the end of storage, assessed by the trypan blue technique, was 1.47% (SD 2.63, range 0.03–12); assessed by the TUNEL technique it was 12.7% (SD 16.4 range 0.6–65.5). There was a significant correlation between the two techniques (r = 0.7, p<0.001). The percentage of TUNEL stained ECs was correlated negatively with EC density at the end of storage (r = −0.47, p <0.005) and positively with percentage EC loss during storage (r = 0.46, p < 0.05). Conclusion: This study demonstrates that organ cultured corneas systematically carry non-viable ECs that are implicated in cell death by apoptosis and go undetected when trypan blue staining is used. Because the in situ TUNEL assay detects earlier events in the cell death process than does trypan blue, it should be used to quantify endothelial viability, especially for experiments with new storage media.

Visual outcome and prognostic factors after magnetic extraction of posterior segment foreign bodies in 40 cases

AIMS To evaluate the clinical features as well as the visual and anatomical outcome in eyes with magnetic posterior segment foreign bodies, to identify prognostic factors after removal using an electromagnet. METHODS The records of 40 patients with posterior segment foreign bodies were retrospectively reviewed for 6 years (1989–94). Post-traumatic cataracts and secondary retinal detachments were treated using conventional surgical techniques. Pars plana vitrectomy was used only for late complications. The mean follow up was 30 months (6–71). Clinical factors were studied using univariate analysis. RESULTS The most common findings before treatment of these 40 eyes were lens wound, hyphaema, vitreous haemorrhage, and retinal impairment. The foreign body was in the vitreous (85%) or minimally embedded in the retina (15%). Initial visual acuity was worse or equal to 20/40 in 70% of the cases. Subsequent to surgical treatment, a cataract was reported in 60% of the patients. Postoperative complications included retinal detachment (15%) and phthysis (5%). The prognosis was worse in cases with intraocular foreign body of largest diameter ⩾3 mm, an initial visual acuity less than 20/200, or the presence of post-traumatic retinal detachment. Presence of initial intravitreous haemorrhage, hyphaema, or intraocular tissue prolapse did not appear to affect the prognosis. CONCLUSION The long term visual acuity results indicated that wound repair associated with conventional magnet extraction in an emergency is a viable treatment for posterior segment magnetic foreign bodies in this selected group. At the time of diagnosis, size of foreign body (<3 mm) and initial visual acuity ⩾20/200 were predictors of good visual outcome after primary magnetic extraction.

Incidence of Acute Postoperative Endophthalmitis after Cataract Surgery: A Nationwide Study in France from 2005 to 2014.

PURPOSE To report the incidence of acute postoperative endophthalmitis (POE) after cataract surgery from 2005 to 2014 in France. DESIGN Cohort study. PARTICIPANTS Patients undergoing operation for cataract surgery by phacoemulsification and presenting acute POE. METHODS We identified acute POE occurring within 6 weeks after phacoemulsification cataract surgery and the use of intracameral antibiotic injection during the surgical procedure by means of billing codes from a national database. MAIN OUTCOME MEASURES Incidence of acute POE. RESULTS From January 2005 to December 2014, 6 371 242 eyes in 3 983 525 patients underwent phacoemulsification cataract surgery. The incidence of acute POE after phacoemulsification decreased from 0.145% to 0.053% during this 10-year period; the unadjusted incidence rate ratio (IRR) (95% confidence interval) was 0.37 (0.32-0.42; P < 0.001). In multivariate analysis, intracameral antibiotic injection was associated with a lower risk of acute POE 0.53 (0.50-0.57; P < 0.001), whereas intraoperative posterior capsule rupture, combined surgery, and gender (male) were associated with a higher risk of acute POE: 5.24 (4.11-6.68), 1.77 (1.53-2.05), and 1.48 (1.40-1.56) (P < 0.001), respectively. CONCLUSIONS Access to a national database allowed us to observe a decrease in acute POE after phacoemulsification cataract surgery from 2005 to 2014. Within the same period, the use of intracameral antibiotics during the surgical procedures increased.

Acute posterior multifocal placoid pigment epitheliopathy associated with Wegener's granulomatosis.

PURPOSE To report acute posterior multifocal placoid pigment epitheliopathy (APMPPE) in the course of systemic Wegeners granulomatosis. METHODS A complete ophthalmologic evaluation was undertaken, including fluorescein and indocyanine green angiography. RESULTS Two patients diagnosed with Wegeners granulomatosis developed multiple white-yellow subretinal areas with smooth margins typical of APMPPE. Case 1 presented with bilateral choroidal involvement and a granulomatous anterior uveitis. In Case 2, placoid lesions were diagnosed 2 months after onset of systemic Wegeners granulomatosis. In both cases, fluorescein angiography showed an early hypofluorescence and a late staining of the lesions. Indocyanine green angiography revealed early and late hypofluorescence corresponding to the areas seen clinically. Wegeners granulomatosis was diagnosed histologically in both cases. After combined steroid and cyclophosphamide therapy, the lesions healed, and after a follow-up period of 1.5 and 4 years, respectively, funduscopic and angiographic examinations showed cicatricial lesions. CONCLUSION Acute posterior multifocal placoid pigment epitheliopathy is a rare manifestation of Wegeners granulomatosis and should be considered a possible systemic involvement of the disease. A prompt, thorough investigation should be undertaken for an underlying systemic disorder.

Mechanisms of staurosporine induced apoptosis in a human corneal endothelial cell line

Background: Apoptosis very probably plays a key part in endothelial cell loss during corneal storage in organ culture as well as hypothermic storage. However, the mechanisms underlying endothelial apoptosis are poorly understood. The response of a human corneal endothelial cell (HCEC) line to staurosporine, a known inducer of apoptosis, was investigated to gain insights into the intracellular modulators that participate in endothelial cell death. Methods: Immortalised HCECs were studied after 3, 6, 12, and 24 hours of incubation with 0.2 μM staurosporine. Cell shedding was monitored. Hoechst 33342 fluorescent DNA staining combined with propidium iodide was used for apoptosis/necrosis quantification and morphological examination. The caspase-3 active form was assessed using western blot, proteolytic activity detection, and immunocytochemistry. The cleaved form of poly(ADP-ribose) polymerase (PARP) was assessed using immunocytochemistry and western blot. The ultrastructural features of cells were screened after 12 hours with staurosporine or vehicle. Results: The specific apoptotic nature of staurosporine induced HCEC death was confirmed. The ultrastructural features of staurosporine treated cells were typical of apoptosis. HCEC shedding and DNA condensation increased with time. Caspase-3 activity was detected as early as 3 hours after exposure with staurosporine, peaking at 12 hours of incubation. The presence of cleaved PARP after 3 hours confirmed caspase-3 activation. Conclusions: These data suggest strongly that HCEC cell death induced by staurosporine is apoptosis. The main consequence of HCEC apoptosis is shedding. Staurosporine induced apoptosis of endothelial cells involves activation of caspase-3, and could be a useful model to study strategies of cell death inhibition.