David Gaucher

Dome-Shaped Macula in Eyes with Myopic Posterior Staphyloma

PURPOSEnTo describe an unusual feature in myopic eyes responsible for visual loss, which we call a dome-shaped macula.nnnDESIGNnRetrospective, observational case series.nnnMETHODSnAfter observing isolated cases of dome-shaped macula, we analyzed optical coherence tomography (OCT) scans of 140 highly myopic eyes present in our OCT database to find similar cases. Fifteen eyes of 10 patients had a dome-shaped macula. These patients all had undergone fluorescein angiography (FA), indocyanine green angiography (ICGA), and B-scan ultrasonography examinations.nnnRESULTSnThe mean refractive error of the affected eyes was -8.25 diopters (D; range, -2 to -15 D). Median visual acuity was 20/50. Recent visual impairment was noted in 11 of the 15 eyes studied, and metamorphopsia was noted in eight eyes. Four eyes were asymptomatic. FA showed atrophic changes in the macular retinal pigment epithelium (RPE) in all eyes, combined with focal points of leakage in seven of the 15 eyes. The dome-shaped appearance of the macula was visible on both B-scan ultrasonography and OCT: a characteristic bulge of the macular retina, RPE, and choroid within the concavity of the moderate posterior staphyloma was present in all eyes. In 10 eyes, OCT also showed a shallow foveal detachment at the top of the dome-shaped macula.nnnCONCLUSIONSnA dome-shaped macula within a myopic staphyloma is an unreported type of myopic posterior staphyloma. The dome-shaped macula often is associated with RPE atrophic changes and foveal retinal detachment, which may explain the visual impairment in these eyes.

Microglial changes occur without neural cell death in diabetic retinopathy

Very early neuroglial changes have been observed to precede major vascular changes in the retina of diabetic patients and animal models. We investigated the sequence of these neuroglial changes further, in mice with alloxan-induced diabetes. Diabetes was induced by a single injection of Alloxan into C57/Bl6 mice, which subsequently received daily insulin injections. Diabetic and control animals were weighed and their blood glucose levels were determined weekly. Electroretinographic recordings and scanner laser ophthalmoscope (SLO) examinations were carried out 15 days, one month and three months after the onset of diabetes. Diabetes induction was confirmed by the presence of glucose in the urine, a tripling of blood glucose level, weight loss and an increase in glycated haemoglobin levels. Three months after diabetes onset, the electroretinogram b/a wave amplitude ratio was decreased at the highest light intensities and oscillatory potentials were delayed. The retinal fundus and vessels remained unchanged. No cell apoptosis was detected in vertical and horizontal sections of the retina by TUNEL or immunocytochemistry for the active caspase 3. No increase in GFAP-immunostaining indicative of a glial reaction was observed in Müller glial cells. By contrast, changes in the morphology of microglial cells were observed, with marked shortening of the dendrites. Thus, the microglial reaction occurs very early in progression to diabetic retinopathy, at about the same time as early electroretinographic modifications. The absence of apoptotic cells, contrasting with previous results in mice with streptozotocin-induced diabetes, is consistent with insulin neuroprotection.

Increased Vitreous Shedding of Microparticles in Proliferative Diabetic Retinopathy Stimulates Endothelial Proliferation

OBJECTIVE Diabetic retinopathy is associated with progressive retinal capillary activation and proliferation, leading to vision impairment and blindness. Microparticles are submicron membrane vesicles with biological activities, released following cell activation or apoptosis. We tested the hypothesis that proangiogenic microparticles accumulate in vitreous fluid in diabetic retinopathy. RESEARCH DESIGN AND METHODS Levels and cellular origin of vitreous and plasma microparticles from control (n = 26) and diabetic (n = 104) patients were analyzed by flow cytometry, and their proangiogenic activity was assessed by in vitro thymidine incorporation and neovessel formation in subcutaneous Matrigel plugs in mice. RESULTS Microparticles of endothelial, platelet, photoreceptor, and microglial origin were identified in vitreous samples. Levels of photoreceptor and microglial microparticles were undetectable in plasmas but were comparable in diabetic and control vitreous samples. Vitreous platelet and endothelial microparticles levels were increased in diabetic patients and decreased following panretinal laser photocoagulation or intravitreal antivascular endothelial growth factor injection in proliferative diabetic retinopathy (PDR). The ratio of vitreous to plasma microparticle levels was calculated to estimate local formation versus potential plasma leakage. In PDR, the endothelial microparticles ratio—but not that for platelet—was greater than 1.0, indicating local formation of endothelial microparticles from retinal vessels and permeation of platelet microparticles from plasma. Isolated vitreous microparticles stimulated by 1.6-fold endothelial proliferation and increased new vessel formation in mice. CONCLUSIONS The present study demonstrates that vitreous fluid contains shed membrane microparticles of endothelial, platelet, and retinal origin. Vitreous microparticles levels are increased in patients with diabetic retinopathy, where they could contribute to disease progression.

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.

Taurine: The comeback of a neutraceutical in the prevention of retinal degenerations

Taurine is the most abundant amino acid in the retina. In the 1970s, it was thought to be involved in retinal diseases with photoreceptor degeneration, because cats on a taurine-free diet presented photoreceptor loss. However, with the exception of its introduction into baby milk and parenteral nutrition, taurine has not yet been incorporated into any commercial treatment with the aim of slowing photoreceptor degeneration. Our recent discovery that taurine depletion is involved in the retinal toxicity of the antiepileptic drug vigabatrin has returned taurine to the limelight in the field of neuroprotection. However, although the retinal toxicity of vigabatrin principally involves a deleterious effect on photoreceptors, retinal ganglion cells (RGCs) are also affected. These findings led us to investigate the possible role of taurine depletion in retinal diseases with RGC degeneration, such as glaucoma and diabetic retinopathy. The major antioxidant properties of taurine may influence disease processes. In addition, the efficacy of taurine is dependent on its uptake into retinal cells, microvascular endothelial cells and the retinal pigment epithelium. Disturbances of retinal vascular perfusion in these retinal diseases may therefore affect the retinal uptake of taurine, resulting in local depletion. The low plasma taurine concentrations observed in diabetic patients may further enhance such local decreases in taurine concentration. We here review the evidence for a role of taurine in retinal ganglion cell survival and studies suggesting that this compound may be involved in the pathophysiology of glaucoma or diabetic retinopathy. Along with other antioxidant molecules, taurine should therefore be seriously reconsidered as a potential treatment for such retinal diseases.

Treatment of exudative age-related macular degeneration with a designed ankyrin repeat protein that binds vascular endothelial growth factor: a phase I/II study.

PURPOSEnTo evaluate the safety, tolerability and bioactivity of ascending doses of MP0112, a designed ankyrin repeat protein (DARPin) that binds with high affinity to vascular endothelial growth factor-A (VEGF-A), in treatment-naive patients with exudative age-related macular degeneration (AMD).nnnDESIGNnPhase I/II, open-label, multicenter, dose-escalation study.nnnMETHODSnPatients were to receive a single intravitreal injection of MP0112 at doses ranging from 0.04 to 3.6 mg and be monitored for 16 weeks for safety, efficacy, pharmacokinetics, and dose response.nnnRESULTSnAltogether, 32 patients received a single injection of MP0112. The maximum tolerated dose was 1.0 mg because of a case of endophthalmitis in the 2.0 mg cohort. Drug-related adverse events were reported by 13 (41%) of 32 patients; they included ocular inflammation in 11 patients (7 mild, 4 moderate in severity). Visual acuity scores were stable or improved compared with baseline for ≥4 weeks following injection; both retinal thickness and fluorescein angiography leakage decreased in a dose-dependent manner. Rescue therapy was administered to 20 (91%) of 22 patients who received 0.04-0.4 mg MP0112 compared with 4 of 10 (40%) patients who received 1.0 or 2.0 mg. Of patients in the higher-dose cohorts who did not require rescue treatment, 83% (5/6) maintained reductions in central retinal thickness through week 16.nnnCONCLUSIONSnA single injection of 1.0 or 2.0 mg MP0112 resulted in mean decreases in retinal thickness and leakage area despite ocular inflammation. Larger-scale studies are warranted to confirm these observations.

Taurine deficiency damages retinal neurones: cone photoreceptors and retinal ganglion cells

In 1970s, taurine deficiency was reported to induce photoreceptor degeneration in cats and rats. Recently, we found that taurine deficiency contributes to the retinal toxicity of vigabatrin, an antiepileptic drug. However, in this toxicity, retinal ganglion cells were degenerating in parallel to cone photoreceptors. The aim of this study was to re-assess a classic mouse model of taurine deficiency following a treatment with guanidoethane sulfonate (GES), a taurine transporter inhibitor to determine whether retinal ganglion cells are also affected. GES treatment induced a significant reduction in the taurine plasma levels and a lower weight increase. At the functional level, photopic electroretinograms were reduced indicating a dysfunction in the cone pathway. A change in the autofluorescence appearance of the eye fundus was explained on histological sections by an increased autofluorescence of the retinal pigment epithelium. Although the general morphology of the retina was not affected, cell damages were indicated by the general increase in glial fibrillary acidic protein expression. When cell quantification was achieved on retinal sections, the number of outer/inner segments of cone photoreceptors was reduced (20xa0%) as the number of retinal ganglion cells (19xa0%). An abnormal synaptic plasticity of rod bipolar cell dendrites was also observed in GES-treated mice. These results indicate that taurine deficiency can not only lead to photoreceptor degeneration but also to retinal ganglion cell loss. Cone photoreceptors and retinal ganglion cells appear as the most sensitive cells to taurine deficiency. These results may explain the recent therapeutic interest of taurine in retinal degenerative pathologies.

Long-term outcomes of acute traumatic maculopathy.

Purpose: To report immediate and long-term outcomes of acute traumatic maculopathy. Methods: Retrospective case series. Acute traumatic maculopathy was defined as a macular opacification after blunt trauma. Patients were examined at presentation, 1 week, and 6 months. Retinography and time-domain and spectral-domain optical coherence tomographies were performed in all patients. Central macular thickness, the qualitative aspect of the macular profile, and retinal nerve fiber layer thickness were assessed. Multifocal electroretinography was performed at presentation and after 6 months. Results: Twenty patients (20 eyes) were studied. Their mean age was 20.8 years, and the initial visual acuity was 20/100. In all cases, initial optical coherence tomographies revealed an increase in reflectivity of the inner and outer segment junction, with an apposition of the latter to the retinal pigment epithelium. Optical coherence tomography profiles were back to normal at the 1-week visit. Initial multifocal electroretinography performed in six patients showed a decrease in amplitudes in the central area but not in the periphery. There was no delay in latency. Similar electroretinal dysfunction persisted after 6 months. Conclusion: Macular opacification observed in acute traumatic maculopathy is associated with an increase in reflectivity of the inner and outer segment photoreceptor junction on optical coherence tomography. Although visual recovery is excellent, reduction in the electroretinal activity observed 6 months after the trauma suggests that the retina does not fully recover from the initial disorganization of its external layers.

Use of digital camera imaging of eye fundus for telemedicine in children suspected of abusive head injury

Aim: Pilot study of the role of RetCam imaging for telemedicine in lieu of availability of ophthalmologist examination for cases of suspected abusive head injury. Design: Cross-sectional observational study. Participants: 21 children admitted in the paediatric units of the University Hospital of Strasbourg (France) with suspicion of abusive head trauma were included. Methods: Children were examined by standard ophthalmoscopy. Photographs were taken using the RetCam-120 Digital Retinal Camera. Eye fundus images were stored and remotely read by an ophthalmologist. Patients also had radiographic skeletal series to look for bone fractures, and CT scan and/or MRI of the head to look for intracranial haemorrhages. Main outcome measures: The absence or presence of retinal haemorrhages was assessed by both methods. Feasability, sensitivity and specificity of the digital camera procedure were determined. Results: 85.7% of the children presented cerebral bleeding, and 14 out of the 21 (66.7%) had retinal haemorrhages on ophthalmoscopy. The digital camera detected the retinal abnormalities in all cases. One false-positive case was also reported. The sensitivity of the digital camera detection method was 100% with a specificity of 85.7%. 14 patients were eventually diagnosed as suffering from abusive trauma. RetCam helped establishing the diagnosis of abuse in 92.8% of these cases. Conclusions: Digital photography compared with ophthalmoscopy has a good sensitivity and specificity in detecting retinal haemorrhages. Remote reading of RetCam-120 photographs could be a promising strategy in detecting children with abusive head trauma.

Taurine Is a Crucial Factor to Preserve Retinal Ganglion Cell Survival

Retinal ganglion cells (RGCs) are spiking neurons, which send visual information to the brain, through the optic nerve. RGC degeneration occurs in retinal diseases, either as a primary process or secondary to photoreceptor loss. Mechanisms involved in this neuronal degeneration are still unclear and no drugs directly targeting RGC neuroprotection are yet available. Here, we show that taurine is one factor involved in preserving the RGC survival. Indeed, a taurine depletion induced by the antiepileptic drug, vigabatrin, was incriminated in its retinal toxicity leading to the RGC loss. Similarly, we showed that RGC degeneration can be induced by pharmacologically blocking the taurine-transporter with the chronic administration of a selective inhibitor, which results in a decrease in the taurine levels both in the plasma and in the retinal tissue. Finally, we found that taurine can directly prevent RGC degeneration, occurring either in serum-deprived pure RGC cultures or in animal models presenting an RGC loss (glaucomatous rats and the P23H rats, a model for retinitis pigmentosa). These data suggest that the retinal taurine level is a crucial marker to prevent RGC damage in major retinal diseases.