[Management of ocular toxoplasmosis in France: Results of a modified Delphi study]. / Prise en charge de la toxoplasmose oculaire en France : résultats d'une étude Delphi modifiée.

OBJECTIVE: To evaluate diagnostic and therapeutic practices and then establish a consensus on the management of ocular toxoplasmosis in France through a Delphi study. MATERIALS AND METHODS: Twenty-three French experts in ocular toxoplasmosis were invited to respond to a modified Delphi study conducted online, in the form of two questionnaires, in an attempt to establish a consensus on the diagnosis and management of this pathology. The threshold for identical responses to reach consensus was set at 70 %. RESULTS: The responses of 19 experts out of the 23 selected were obtained on the first questionnaire and 16 experts on the second. The main elements agreed upon by the experts were to treat patients with a decrease in visual acuity or an infectious focus within the posterior pole, to treat peripheral lesions only in the presence of significant inflammation, the prescription of first-line treatment with pyrimethamine-azithromycin, the use of corticosteroid therapy after a period of 24 to 48hours, the prophylaxis of frequent recurrences (more than 2 episodes per year) with trimethoprim-sulfamethoxazole as well as the implementation of prophylactic treatment of recurrences in immunocompromised patients. On the other hand, no consensus emerged with regard to the examinations to be carried out for the etiological diagnosis (anterior chamber paracentesis, fluorescein angiography, serology, etc.), second-line treatment (in the case of failure of first-line treatment), or treatment of peripheral foci. CONCLUSION: This study lays the foundations for possible randomized scientific studies to be conducted to clarify the management of ocular toxoplasmosis, on the one hand to confirm consensual clinical practices and on the other hand to guide practices for which no formal consensus has been demonstrated.

[Retinal vascular network: Changes with aging and systemic vascular disease (cardiac and cerebral)]. / Caractéristiques vasculaires rétiniennes : modifications lors du vieillissement et en pathologie vasculaire systémique (cardiaque et cérébrale).

For over 10 years, the description of the retinal microvascular network has benefited from the development of new imaging techniques. Automated retinal image analysis software, as well as OCT angiography (OCT-A), are able to highlight subtle, early changes in the retinal vascular network thanks to a large amount of microvascular quantitative data. The challenge of current research is to demonstrate the association between these microvascular changes, the systemic vascular aging process, and cerebrovascular and cardiovascular disease. Indeed, a pathophysiological continuum exists between retinal microvascular changes and systemic vascular diseases. In the Montrachet study, we found that a suboptimal retinal vascular network, as identified by the Singapore I Vessel Assessment (SIVA) software, was significantly associated with treated diabetes and an increased risk of cardiovascular mortality. In addition, we supplemented our research on the retinal vascular network with the use of OCT-A. In the EYE-MI study, we showed the potential role of quantitative characterization of the retinal microvascular network by OCT-A in order to assess the cardiovascular risk profile of patients with a history of myocardial infarction. A high AHA (American Heart Association) risk score was associated with low retinal vascular density independently of hemodynamic changes. Thus, a better understanding of the association between the retinal microvasculature and macrovascular disease might make its use conceivable for early identification of at-risk patients and to suggest a personalized program of preventative care. The retinal vascular network could therefore represent an indicator of systemic vascular disease as well as an interesting predictive biomarker for vascular events.

Twelve-month outcomes of intra-vitreal anti-VEGF agents for treatment-naïve neovascular age-related macular degeneration eyes: French data from the fight for retinal blindness!

INTRODUCTION: To describe the one-year functional outcomes of treatment-naïve neovascular age-related macular degeneration (nAMD) treated with anti-VEGF agents at the Dijon University Hospital Ophthalmology Department. METHODS: Real-life interventional study including all treatment-naïve nAMD patients from January 2016 to December 2018 in the Ophthalmology Department of Dijon University Hospital. Data were retrospectively collected from the Fight Retinal Blindness! (FRB!) registry. At baseline, medical history, visual acuity (VA), type of lesion and activity on angiography and optical coherence tomography (OCT), and treatment were recorded. On follow-up, VA, lesion activity and treatment were recorded. RESULTS: Three-hundred twenty eyes of 259 patients were included, of which 65.6% were female and with a mean age of 80.1±11.1 years. Mean VA (standard deviation, SD) at baseline was 53.2 ETDRS letters (25.3). All patients received anti-VEGF injections, of which 164 eyes (51.2%), 152 eyes (47.5%) and 4 eyes (1.2%) were treated with aflibercept, ranibizumab and bevacizumab, respectively. A total of 198 eyes of 169 patients completed the 12-month follow-up, with a median (first quartile, third quartile) of 12 visits (10, 13). At one year (n=198), the overall mean VA gain [95% CI] was +3.3 ETDRS letters [0.7, 5.9] and 173 (87.4%) of the treated eyes did not lose 15 or more letters. We found no statistically significant difference in mean VA gain between aflibercept and ranibizumab. CONCLUSION: This real-world study confirmed the efficacy of anti-VEGF agents in nAMD and the feasibility of analyzing data in an international registry.

Efficacy and follow-up of anti-VEGF injections in diabetic macular edema in real-life practice at the Dijon university medical centre through the Save Sight Registries.

PURPOSE: To evaluate the efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections (IVT) in diabetic macular edema (DME) in real-life practice using the Save Sight Registries (SSR). MATERIAL AND METHODS: We conducted an observational, single-centre, retrospective study in the department of ophthalmology of the Dijon University Hospital. We included treatment-naive patients who presented with DME between January 2016 and December 2017. Demographic and clinical data, follow-up visits, and treatments administered were entered into the SSR, an international online ophthalmic registry. Primary endpoints were the change in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline to 12 and 24 months. RESULTS: Fifty-eight eyes of 43 patients with a mean [standard deviation (SD)] age of 67.1 [9.5] years were included. Forty-one eyes completed 12 months of follow-up, and 17 eyes completed 24 months of follow up. Median [SD] baseline BCVA was 56.1 [22.9] ETDRS letters and the median [95% confidence interval (95% CI)] baseline CST was 447.9 [161.0] micrometers (µm). Median [95% CI] improvement in BCVA from baseline to months 12 and 24 were respectively, +5.6 [+0.5; +10.7] ETDRS letters and +7.7 [-2.8; +18.2] ETDRS letters. The median [95% CI] decrease in CST from baseline to months 12 and 24 were respectively, -110.9 [-154.5; -67.3] µm and -125.5 [-198.0; -53.0] µm. CONCLUSION: Our clinical practice can be evaluated easily with the SSR system. In real life, anti-VEGF IVT are an effective treatment for DME, which result in improved BCVA and decreased CST.

Evaluation of the Spot Vision Screener in comparison with the orthoptic examination in visual screening in 3-5 year-old schoolchildren.

PURPOSE: To evaluate the Spot Vision Screener (SVS) compared with the orthoptic examination for detection of amblyopia risk factors in preschools. METHODS: This prospective study included children with a visual screening organized by the department of "le" (PMI) in Côte d'Or (Burgundy, France), between June 2017 and April 2018. All children were evaluated with the SVS followed by a clinical orthoptic examination. Results with the SVS were compared with those obtained by clinical orthoptic examination. RESULTS: A total of 1236 subjects were included in the study from 100 preschools. The mean age of the children was 3.6±0.7 years, and 627 were female (50.7%). The orthoptic examination detected 308 (24.9%) children with subnormal visual acuity for age in one eye or both. In children with a history of prematurity, the orthoptic examination was more frequently abnormal (P=0.002), which was not seen with the SVS (P=0.050). The SVS screened 20 (1.6%) children with strabismus, while 40 (3.2%) were detected by orthoptic examination. At the end of the screening, the SVS detected 182 (14.7%) suspect patients while 311 (25.1%) suspect patients were detected after the orthoptic examination. Comparing SVS with orthoptic examination, agreement was fair (κ=0.4). CONCLUSION: The SVS can be a useful device for visual screening, but agreement with the orthoptic examination was only fair. The Spot vision screener should be used in conjunction with a clinical orthoptic examination.

Influence of cardiac hemodynamic variables on retinal vessel density measurement on optical coherence tomography angiography in patients with myocardial infarction.

INTRODUCTION: Quantitative measurements of retinal microvasculature by optical coherence tomography angiography (OCT-A) have been used to assess cardiovascular risk profile. However, to date, there are no studies focusing on OCT-A imaging in the setting of the altered hemodynamic status found in high-risk cardiovascular patients. METHODS: To determine the potential association between retinal vascular density on OCT-A and a comprehensive battery of hemodynamic variables in patients with myocardial infarction (MI) using data from the acute phase and at 3 months follow-up after cardiac rehabilitation. This prospective longitudinal study included patients who presented with MI in the cardiology intensive care unit at Dijon University Hospital. Main outcomes and measurements were retinal vessel density on OCT-A, hemodynamic status based on left ventricular ejection fraction (LVEF), and indexed cardiac output during the acute phase of myocardial infarction and at 3 months follow-up. RESULTS: Overall, 30 patients were included in this pilot study. The median (IQR) age was 64 years (55-71) with 87% men. At admission, the mean (SD) LVEF was 53% (11), and the mean indexed cardiac output was 2.70 (0.83) L/min/m2. On OCT-A, the mean inner retinal vascular density was 19.09 (2.80) mm-1. No significant association was found between retinal vascular density and hemodynamic variables. CONCLUSION: We found no significant association between retinal vascular density on OCT-A and hemodynamic variables in the acute phase of a myocardial infarction or after 3 months of cardiac rehabilitation. Therefore, OCT-A findings do not seem to be influenced by the hemodynamic changes associated with myocardial infarction.

[Use of biotherapy in the management of Behçet's disease in a department of internal medicine]. / Recours à la biothérapie dans la prise en charge de la maladie de Behçet dans un service de médecine interne.

BACKGROUND: Behçet's disease (BD) is a recurrent multisystemic disease responsible for occlusive vasculitis with arterial, venous and capillary involvement. The aim of this study was to determine the frequency and the features associated with the use of biotherapy in the management of patients followed in our department for BD. METHODS: This is a retrospective study of patients medical records followed for BD in a department of internal medicine from January 2005 to August 2018. RESULTS: A total of 41 patients were included with a mean age at diagnosis of 42.5±12.1 years (range 16 to 63) and a sex ratio men/women of 1.05. Oral and/or genital aphtosis was present in 70.7% of the patients. Other lesions were: ocular (78.0%), articular (46.3%), cutaneous (41.5%), central neurological (34.1%), vascular (26.8%), digestive (7.3%), pericardial (2.4%) and epididymal (2.4%). A biotherapy, interferon α and monoclonal antibodies, was used in 15 patients (36.6%), after failure of conventional treatments. The monoclonal antibodies were anti-TNFα (infliximab, adalimumab, certolizumab and golimumab) except in one patient for whom ustekinumab was used. Biotherapy was used in 46.9% of the patients with ocular involvement and never used in those patients without ocular involvement (P=0.01). CONCLUSION: Biotherapy is effective and represents a solution to the failures of conventional treatments in severe forms of Behçet's disease with ocular involvement.

Visual outcomes and complications of congenital cataract surgery.

PURPOSE: To describe the visual results and postoperative complications of congenital cataract surgeries performed between 2005 and 2016. METHODS: A retrospective consecutive case series of congenital cataract surgeries was carried out at the Dijon University Hospital in France. Intraocular lens implantation was primary or secondary according to age. Pre- and post-operative assessment was performed through ophthalmologic consultations with orthoptic measurements. Visual function and adverse events were recorded. RESULTS: Fifty-six consecutive procedures were evaluated in 37 infants. Overall, 26.8% of patients had unilateral cataracts, and 73.2% had bilateral cataracts. Median age at surgery was 1.0 years [IQR (interquartile range): 0.3-5.2] and 2.7 years [IQR: 0.4-9.5] for unilateral and bilateral cataracts, respectively. Median best-corrected visual acuity (BCVA) at the last follow-up was 0.5logMAR [IQR: 0.2-0.8] and 0.1logMAR [IQR: 0.0-0.8] for the unilateral and bilateral group, respectively. Posterior capsule opacification (PCO) was the primary postoperative complication: 60.0% in unilateral cataract and 46.3% in bilateral cataracts (P=0.019). Median follow-up was 2.0 years [IQR: 1.0-5.0]. CONCLUSION: Congenital cataract surgery appears to be safe and effective when combined with early, conscientious amblyopia treatment. Bilateral congenital cataracts had better visual outcome than unilateral cataract.

Basal Tear Osmolarity as a metric to estimate body hydration and dry eye severity.

The osmolarities of various bodily fluids, including tears, saliva and urine, have been used as indices of plasma osmolality, a measure of body hydration, while tear osmolarity is used routinely in dry eye diagnosis, the degree of tear hyperosmolarity providing an index of disease severity. Systemic dehydration, due to inadequate water intake or excessive water loss is common in the elderly population, has a high morbidity and may cause loss of life. Its diagnosis is often overlooked and there is a need to develop a simple, bedside test to detect dehydration in this population. We hypothesize that, in the absence of tear evaporation and with continued secretion, mixing and drainage of tears, tear osmolarity falls to a basal level that is closer to that of the plasma than that of a tear sample taken in open eye conditions. We term this value the Basal Tear Osmolarity (BTO) and propose that it may be measured in tear samples immediately after a period of evaporative suppression. This value will be particular to an individual and since plasma osmolarity is controlled within narrow limits, it is predicted that it will be stable and have a small variance. It is proposed that the BTO, measured immediately after a defined period of eye closure, can provide a new metric in the diagnosis of systemic dehydration and a yardstick against which to gauge the severity of dry eye disease.

[Eye and cat scratch disease: A case series]. / Œil et maladie des griffes du chat : à propos de 7 cas.

INTRODUCTION: Cat scratch disease is a pleiomorphic condition, sometimes with isolated ophthalmic involvement. We report the clinical observations of seven cases with ophthalmologic manifestations of cat scratch disease. OBSERVATIONS: There were seven patients, with a median age of 52 years, of whom five were women and three had unilateral involvement. Six exhibited Leber's stellate neuroretinitis, an incomplete syndrome in two cases, and one associated with chorioretinal foci. One patient had isolated retinal infiltrates. The diagnosis of cat scratch disease was confirmed by Bartonella henselae serology, positive in all cases. All patients received treatment with doxycycline. Ocular complications (with optic atrophy and macular retinal pigment epithelial changes) were noted in five cases. DISCUSSION: Ocular bartonellosis is an atypical clinical form. It requires a directed ancillary work-up with serology or PCR, which has the peculiarity of being highly specific if not very sensitive. Treatment is above all preventive. Antibiotics may be initiated. CONCLUSION: Cat scratch disease must be excluded in the work-up of posterior uveitis.

Clinical spectrum of eye malformations in four patients with Mowat-Wilson syndrome.

Mowat-Wilson syndrome (MWS) is a rare genetic syndrome characterized by a specific facial gestalt, intellectual deficiency, Hirschsprung disease and multiple congenital anomalies. Heterozygous mutations or deletions in the zinc finger E-box-binding homeobox2 gene (ZEB2) cause MWS. ZEB2 encodes for Smad-interacting protein 1, a transcriptional co-repressor involved in TGF-beta and BMP pathways and is strongly expressed in early stages of development in mice. Eye abnormalities have rarely been described in patients with this syndrome. Herein, we describe four patients (two males and two females; mean age 7 years) with MWS and eye malformations. Ocular anomalies included, iris/retinal colobomas, atrophy or absence of the optic nerve, hyphema, and deep refraction troubles, sometimes with severe visual consequences. All eye malformations were asymmetric and often unilateral and all eye segments were affected, similarly to the nine MWS cases with ophthalmological malformations previously reported (iris/chorioretinal/optic disc coloboma, optic nerve atrophy, retinal epithelium atrophy, cataract, and korectopia). In human embryo, ZEB2 is expressed in lens and neural retina. Using the present report and data from the literature, we set out to determine whether or not the presence of eye manifestations could be due to specific type or location of mutations. We concluded that the presence of eye malformations, although a rare feature in MWS, should be considered as a part of the clinical spectrum of the condition.

Intravitreal dexamethasone implant versus anti-VEGF injection for treatment-naïve patients with retinal vein occlusion and macular edema: a 12-month follow-up study.

PURPOSE: The objective of his study was to compare the visual and anatomical outcomes in treatment-naïve patients with macular edema secondary to retinal vein occlusion after intravitreal injections of dexamethasone implants (DEX) and anti-VEGF. METHODS: One hundred two patients (64 in the anti-VEGF group, 38 in the DEX group) without previous treatment were included in this multi-center retrospective study and evaluated at baseline and 1, 3, 6, and 12 months after the onset of treatment. Patients were defined as "good responders" if central macular thickness (CMT) was less than or equal to 250 µm in TD-OCT or 300 µm in SD-OCT after the injections. RESULTS: At month 3 (n = 102), BCVA had increased significantly, by 0.1 ± 0.3 logMAR in the anti-VEGF group (p = 0.04) and 0.4 ± 0.4 logMAR in the DEX group (p < 0.001); the difference between the two groups was statistically significant (p = 0.007). CMT decreased significantly, by 138 ± 201 µm (-19 %, p < 0.001) in the anti-VEGF group and 163 ± 243 µm (-21 %, p < 0.001) in the DEX group. After 3 months, five patients (13 %) in the DEX group and 20 (31 %) in the anti-VEGF group (p < 0.001) changed treatment. Among the 77 patients who did not switch from their initial treatment, no significant functional or anatomical difference between the two groups was observed at months 6 and 12. Elevation of intraocular pressure > 21 mmHg was more frequent in the DEX group (21 %) than in the anti-VEGF group (3 %, p = 0.008). CONCLUSIONS: Visual acuity recovery was better in the DEX group than in the anti-VEGF group at month 3, but with no difference in CMT. In patients who did not change treatment, the long-term anatomical and visual outcome was similar between the DEX and anti-VEGF groups.

Clinical staining of the ocular surface: mechanisms and interpretations.

In this article we review the mechanism of ocular surface staining. Water-soluble dyes are excluded from the normal epithelium by tight junctions, the plasma membranes and the surface glycocalyx. Shed cells can take up dye. A proportion of normal corneas show sparse, scattered time-dependent, punctate fluorescein uptake, which, we hypothesise, is due to a graded loss of the glycocalyx barrier, permitting transcellular entry into pre-shed cells. In pathological staining, there is little evidence of 'micropooling' at sites of shedding and the term 'punctate erosion' may be a misnomer. It is more likely that the initial event involves transcellular dye entry and, in addition, diffusion across defective tight junctions. Different dye-staining characteristics probably reflect differences in molecular size and other physical properties of each dye, coupled with differences in visibility under the conditions of illumination used. This is most relevant to the rapid epithelial spread of fluorescein from sites of punctate staining, compared to the apparent confinement of dyes to staining cells with dyes such as lissamine green and rose bengal. We assume that fluorescein, with its lower molecular weight, spreads initially by a paracellular route and then by transcellular diffusion. Solution-Induced Corneal Staining (SICS), related to the use of certain contact lens care solutions, may have a different basis, involving the non-pathological uptake of cationic preservatives, such as biguanides, into epithelial membranes and secondary binding of the fluorescein anion. It is transient and may not imply corneal toxicity. Understanding the mechanism of staining is relevant to the standardisation of grading, to monitoring disease and to the conduct of clinical trials.

[Glaucoma medications, preservatives and the ocular surface.] / Traitement du glaucome, conservateurs et surface oculaire.

Several clinical and experimental studies have demonstrated that ocular surface disease is common in glaucoma patients receiving chronic glaucoma drops, and that the preservatives in these drops play a major role in the occurrence of ocular surface disease. These ocular surface changes may induce both symptoms reported by the patients and anterior segment clinical signs, and should be systematically assessed by history and exam in all glaucoma patients. In these patients with ocular surface disease, reducing the amount of preservatives administered to the eye should be strived for, rather than adding additional eye drops to alleviate or mask the side effects of the glaucoma drops.

[Retinal macroaneurysms and macular hemorrhages: report of five cases]. / Macro-anévrismes rétiniens et hémorragies maculaires: à propos de 5 cas.

Retinal macroaneurysm is an uncommon condition, found mainly in hypertensive women over age 60. We report clinical observations in five cases of complicated retinal macroaneurysms. These were all hypertensive women with a mean age of 80.2 years. All retinal macroaneurysms were located in a temporal distribution (superior branch in 80 % of cases), proximal to the third bifurcation, and presented with macular hemorrhage. 4 of the 5 patients were treated surgically by posterior vitrectomy, and one underwent a subretinal injection of recombinant tissue plasminogen activator and gas tamponnade. Functional results were variable. Retinal atrophy secondary to the toxicity of the hemorrhage was observed in two cases. One macular hole was noted.