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.

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.

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.

[Relationship between intravitreal anti-VEGF therapy and subretinal hemorrhage in patients with exudative age-related macular degeneration]. / Relation entre injection intravitréenne d'anti-VEGF et hématome sous-rétinien chez des patients atteints de dégénérescence maculaire liée à l'âge exsudative.

PURPOSE: To assess and compare frequencies and incidence rates of subretinal hemorrhage (SRH) after intravitreal anti-VEGF injections and spontaneous SRH in patients with exudative age-related macular degeneration (AMD). PATIENTS AND METHODS: This retrospective monocentric study included 1079 patients followed for exudative AMD in the ophthalmology department of the university hospital of Dijon from January 2007 to July 2012. For each SRH occuring during this period, the number of previous treatments with intravitreal anti-VEGF was determined, as well as the time between the last injection and the hemorrhage. The SRH was considered as an adverse effect of the anti-VEGF injection if it occurred within 2 months after the last IVT (post-IVT SRH). Frequencies and incidence rates of post-IVT SRH and spontaneous SRH were calculated. RESULTS: Sixty-six SRH's occurred during the study period with a total frequency of 6.12% (CI95% [4.69-7.55]). Frequencies of spontaneous and post-IVT SRH were respectively 5.65% (CI95% [4.28-7.03]) and 0.46% (CI95% [0.06-0.87]), representing a 12.2 ratio. Post-IVT SRH incidence was 8.3/1000 patient-years (CI95% [1.0-15.5]) and the spontaneous SRH incidence rate was 11.6/1000 patient-years (CI95% [8.3-14.8]), (P=0.472). The incidence rate ratio was 0.72 (CI95% [0.29-1.78]). CONCLUSION: This study did not show a statistically significant change in the incidence of SRH after intravitreal anti-VEGF therapy. The benefit/risk ratio of intravitreal anti-VEGF injections for exudative AMD remains high.

RETIDIAB®: assessment of a continuing medical education website for the improvement of diabetic retinopathy management.

AIM: The aim of this study was to evaluate the efficacy of a continuing medical education (CME) website to improve ophthalmological management of diabetic retinopathy (DR). METHODS: A worldwide website called RETIDIAB® was created in which, to log on for first time, users had to take a preliminary test to evaluate their baseline level of knowledge. This allowed them free access to the entire website at any time with no time obligation. The website comprised a course of theoretical concepts and different types of training, including multiple-choice questionnaires (MCQ) focused on the course content, interpretation of diabetic fundus photographs and case reports. After perusing the entire RETIDIAB® website, users could take a second assessment test. Finally, they were asked to fill in a questionnaire evaluating the entire programme. RESULTS: A total of 137 users were registered and, of these, 109 took only the preliminary test, while 28 took the second test and evaluated the entire website; of the latter, 75% were residents and 25% were practising physicians, and 15 were male and 13 were female, ranging in age from 26 to 42 (30.2 ± 3) years. Statistically significant progress was seen between the first and second evaluations (37.3 ± 14% correct answers vs 64 ± 10%, respectively), and the average time interval between the first and second evaluations was 40 ± 20 days. In addition, users expressed a high level of overall satisfaction with the site. CONCLUSION: This pilot study demonstrated the value and effectiveness of RETIDIAB®, a new CME website exclusively devoted to DR management.

[Activity-based financing: is ambulatory care profitable for the institution]. / T2A et chirurgie orbitopalpébrale : l'ambulatoire est-il vraiment rentable pour l'établissement ?

INTRODUCTION: The aim of this study was to evaluate the impact of the 11th version of the National Health System's Activity-Based Financing on the income of a University Hospital department for palpebral, lacrimal, and orbital surgeries. PATIENTS AND METHODS: The number of such surgeries in 2008 was based on the Medicalization Program of the Information System. Using the 11th version of the Activity-Based Financing for Diagnosis-Related Groups, we compared the income in both inpatient and outpatient settings. RESULTS: Two hundred and forty-eight patients undergoing palpebral, lacrimal, or orbital surgery between January and December 2008 were included, with 87% treated on an outpatient basis. The lower reimbursement for outpatient surgery resulted in a loss of 184,500 euros (79%) for our department compared to the inpatient procedure. DISCUSSION: With rigorous organization, ambulatory surgery is feasible for palpebral, lacrimal, and orbital surgery. Nonetheless, with department incomes related to activity, ambulatory care seems financially disadvantageous. Many departments are trying to develop an ambulatory structure, but the need to balance their budget requires improved coherence.

Screening for diabetic retinopathy in a rural French population with a mobile non-mydriatic camera.

AIM: The aim of this study was to evaluate the yield of diabetic retinopathy (DR) screening in a rural population using a mobile non-mydriatic camera. METHODS: The 72 least medicalized areas of Burgundy were the target areas. An orthoptist took fundus photographs using a Topcon TRC-NW6S non-mydriatic camera (four fields: posterior pole; nasal; temporal; and upper). Interpretations were done in the Department of Ophthalmology according to the classification of the French Language Association for the Study of Diabetes and Metabolic Diseases (Alfediam). RESULTS: Between 2004 and 2006, 1974 diabetics were screened-676 the first year, and 1298 in the second. The rate of non-interpretable photographs was 13%. Of the 1974 screened patients, there were 103 cases of DR (5.2%), comprising 70 mild non-proliferative DR (68%), 21 moderate non-proliferative DR (20.4%) and 12 severe non-proliferative DR (11.6%). The mean age of the patients with a DR was 66.7+/-10.9 years, with a mean duration of diabetes of 16.5+/-9.8 years. Only 35 (34%) patients were aware of their HbA(1c), which had a mean value of 7.8% and 19 had visited an ophthalmologist in the year before screening (18.4%). After the initial screening, 90,5% of the patients consulted an ophthalmologist as recommended. CONCLUSION: Screening improved the quality of the ocular follow-up in diabetics in this rural area. However, improvements in management are needed to lower the cost of such a programme.

[Combined glaucoma and diabetic retinopathy screening in Burgundy]. / Dépistage itinérant du glaucome associé à celui de la rétinopathie diabétique en Bourgogne.

INTRODUCTION: The aim of this study was to evaluate the yield of glaucoma and ocular hypertension (OHT) screening in association with diabetic retinopathy (DR) screening in a rural population. PATIENTS AND METHODS: 676 patients were screened between 2004 and 2005. The four departments the Burgundy region were visited, divided into 39 areas with sparse medical services. Each patient had fundus photographs taken with a nonmydriatic camera and IOP measurement in each eye with a noncontact tonometer. Optic discs were classified into suspect or normal. RESULTS: On the 676 screened patients, 41 presented an anomaly (6.1%): 31 with OHT (4.6%), 7 with a suspect optic disc (1.0%), and 3 with both anomalies (0.4%). After further control, we finally found 4 cases of OHT (0.6%) and 8 cases of glaucoma (1.2%). This screening program allowed the diagnosis of 2 new cases of OHT (0.3%) and 4 new cases of glaucoma (0.6%). DISCUSSION: This screening improved the quality of the ophthalmic follow-up in rural areas for diabetics. Furthermore, it is a simple and not more expensive way to screen for OHT and glaucoma in these populations. CONCLUSION: The itinerant screening of OHT and glaucoma combined with a diabetic retinopathy screening is effective. The screening campaign was renewed for 2 years in semi-rural zones.

Measurement of inflammatory cytokines by multicytokine assay in tears of patients with glaucoma topically treated with chronic drugs.

AIM: To investigate the ocular surface inflammatory response to chronic topical treatments in patients with glaucoma by measuring the cytokine level in tears using multiplex bead analysis. METHODS: Tear samples were collected from 21 patients with glaucoma and 12 healthy volunteers. Tears were analysed for the presence of 17 cytokines: interleukin (IL)1beta, IL2, IL4, IL5, IL6, IL7, IL8, IL10, IL12, IL13, IL17, granulocyte-colony stimulating factor, granulocyte-macrophage stimulating factor, interferon (INF)gamma, monocyte chemotactic protein (MCP)1, macrophage inflammatory protein 1beta and tumour necrosis factor (TNF)alpha. The cytokines in each sample of tears were measured using multiplex bead analysis with microspheres as solid support for immunoassays. RESULTS: In the tears of treated patients, proinflammatory cytokines (IL1beta, IL6, IL12, TNFalpha) were significantly increased compared with controls. T helper (Th)1 (INFgamma, IL2) and Th2 (IL5, IL10, IL4) type cytokines were also significantly higher (p<0.05); however, the most marked increase was observed with Th1 cytokines. The expression of chemokine IL8 and MCP1 was also increased in the treated group. CONCLUSION: This study shows that pro-inflammatory cytokine secretion by conjunctival cells is increased in response to topical treatments for glaucoma. The characterisation of cytokines in tears was previously limited by the small volume attainable, a limitation that has been overcome by multiplex analysis.

Trefoil factor family 1, MUC5AC and human leucocyte antigen-DR expression by conjunctival cells in patients with glaucoma treated with chronic drugs: could these markers predict the success of glaucoma surgery?

AIMS: To evaluate conjunctival expression of trefoil factor family (TFF)1, MUC5AC and human leucocyte antigen (HLA)-DR in patients with glaucoma treated with topical drugs, and to determine whether these parameters can predict the outcome of glaucoma surgery. METHODS: 77 conjunctival impression cytology specimens were collected from 77 patients with glaucoma (66 receiving drops with preservative and 11 treated with preservative-free drops) and 43 controls. TFF1, MUC5AC and HLA-DR expression was analysed using flow cytometry. Trabeculectomy was performed in 56 patients; success was defined as an intraocular pressure (IOP) < or =15 mm Hg without any IOP-lowering drug at 6 months. RESULTS: The expression of TFF1, MUC5AC and HLA-DR was significantly higher in patients than in controls (p = 0.01, 0.05 and 0.004, respectively). A higher expression of MUC5AC was found in patients treated with preserved drops than in those receiving unpreserved drops (p = 0.04). A higher MUC5AC expression and a lower HLA-DR expression was observed in successful glaucoma surgeries than in failures. CONCLUSIONS: TFF1 and MUC5AC secretions are probably a response to mild ocular surface changes caused by long-term use of topical treatment. Their increased expression could be a predicting factor of further successful glaucoma surgery.

[Postoperative acute endophthalmitis: a prospective study. Clinical presentation, management and prognostic factors]. / Etude prospective sur les endophtalmies aiguës postopératoires. Description clinique, prise en charge facteurs de risque.

AIMS: To assess the characteristics and visual outcome of patients with acute postoperative endophthalmitis hospitalized in a referral center. MATERIALS AND METHODS: All patients suspected of having infectious endophthalmitis were included in this study. All patients were treated with the same protocol including at least intravitreal injection of antibiotics and instillation of fortified antibiotics. Symptoms, visual acuity, and slit lamp examination were recorded before treatment, at the end of hospitalization and during clinical follow-up. Treatments and biological results were also reported. For patients developing infectious endophthalmitis after cataract surgery, intraoperative management such as location of the incision, suture or sutureless incision, and material of the intraocular lens were also noted. RESULTS: Forty-one patients were included in the study over 32 months (33 patients after cataract surgery). Intraocular inflammation and a decrease in subjective visual acuity were the most frequently reported findings (90% and 94%, respectively). Ocular pain and conjunctiva injection were less frequently reported (47% and 48%, respectively). Symptoms occurred 5 days after the surgery (median); 56% of patients needed a second intravitreal injection of antibiotics. There was a significant increase in visual acuity during and after hospitalization; median final visual acuity was 4.6/10 (0.34 log MAR = 20/43); 30% of patients had less than 20/200, but 44% more than 20/40. In endophthalmitis following cataract surgery, incisions were corneal in all cases and sutured in 62% of cases. Incisions were temporal in 55% of patients. DISCUSSION: Our results are similar to those previously published for acute endophthalmitis following ocular surgery. Intravitreal antibiotic injection remains the gold standard on the management of acute postoperative endophthalmitis.

Blood group related antigens in ocular cicatricial pemphigoid.

AIM: To study the MUC5AC and the blood group related antigen expression in ocular cicatricial pemphigoid (OCP) according to the distribution of Lewis and secretor phenotypes in OCP patients compared to normal subjects. METHODS: Immunostaining was performed on conjunctival biopsy specimens from 22 consecutive patients suffering from OCP, using monoclonal antibodies (Mabs) directed against the peptidic core MUC5AC mucin (anti-M1/MUC5AC Mabs) and against the saccharide moieties (anti-blood group related antigens). These latter included anti-Le(a), anti-Le(b), anti-sialyl Le(a), and H type 2 Mabs, which immunoreact with Lewis positive and non-secretor (Le(a)), Lewis positive and secretor (Le(b)), Lewis positive (sialyl Le(a)), and secretor (H type 2) phenotypes respectively. Serological tests were also performed to confirm the phenotype of each patient. The immunohistopathological patterns and the distribution of Lewis and secretor phenotypes were compared with the results of a previous study in normal individuals. RESULTS: (1) In OCP patients compared to the normal population, anti-M1 immunoreactivity of goblet cells was unchanged, whereas anti-Le(a), anti-Le(b), and anti-sialyl Le(a) immunoreactivities of epithelial and/or goblet cells were markedly decreased. (2) 41% of OCP patients had a non-secretor phenotype, which is statistically significantly more than the estimated incidence of the same phenotype in the French population (20%) (p approximately 0.04). CONCLUSIONS: Mucins in OCP patients showed a decreased expression of blood group related antigens whereas the MUC5AC peptidic core detected by anti-M1 Mab remained unchanged. These results also seem to indicate that OCP may be associated with a non-secretor phenotype.

Alteration of sialyl Lewis epitope expression in pterygium.

PURPOSE: Mucin-related antigens are abundantly expressed by the cells of the normal human conjunctiva. The pattern of these antigens in pterygium, and especially the role of Galbeta1-3GlcNAc alpha2,3-sialyltransferase (ST3Gal III), sialyltransferase necessary to build the sialyl-Le(a) (Lewis(a)) antigen, were studied. METHODS: Immunoperoxidase staining was performed on 28 pterygia using different monoclonal antibodies: anti-M1 (against the peptidic core of gastric mucins encoded by MUC 5AC gene), anti-Le(a)(7LE), anti-sialyl Le(a)(NS 19-9), and anti-Le(b)(2-25LE). A serologic Lewis determination was done in 18 patients. ST3Gal III sialyltransferase expression was also studied in 10 healthy conjunctiva and 10 pterygia by reverse transcriptase-polymerase chain reaction (RT-PCR). Glyceraldehyde-3-phosphate-dehydrogenase was used as an endogenous internal control. RESULTS: First, Le(a), sialyl Le(a), and Le(b) immunoreactivities either decreased or were no longer detectable in pterygium goblet cells as opposed to normal conjunctiva. Second, unlike in pterygium, the Lewis immunoreactivity, which is mainly located in the surface epithelial cells in the normal conjunctiva, was occasionally restricted to the epithelial cells of the deep layers. However, M1 mucins did show an identical pattern expression in a normal conjunctiva and pterygium. ST3Gal III expression was significantly lower in pterygium (0.20+/-0.02 AU [arbitrary units]) than in normal conjunctiva (0.95+/-0.12 AU). CONCLUSIONS: ST3Gal III gene is less expressed in pterygium than in normal conjunctiva. This observation could explain the decrease of sialyl Le(a) expression observed in pterygium by immunohistology.

The ocular penetration of oral sparfloxacin in humans.

The penetration of sparfloxacin into the aqueous humor after oral administration was studied in 28 patients undergoing cataract surgery. Each patient received a single, oral dose of 400 mg of sparfloxacin. In eight other patients scheduled to undergo vitreal surgery, multiple daily oral doses were administered for a total amount of 1,000 mg. The aqueous levels were (mean +/- SEM) 0.127 +/- 0.036 microgram/ml to 0.404 +/- 0.159 microgram/ml from two to 24 hours after ingestion. In the vitreous, the mean drug level was 0.840 microgram/ml (range, 0.480 to 2.060 microgram/ml), from 4.3 to 8.0 hours after the most recent oral dose. Blood samples obtained at the same time as vitreous and aqueous taps were assayed by high-performance liquid chromatography. These data demonstrate that therapeutic levels of sparfloxacin may be achieved in noninflamed, noninfected eyes undergoing cataract or vitreous surgery.