Two-Year Outcome of Aflibercept Intravitreal Injection in Vitrectomized Eyes with Diabetic Macular Edema.

Purpose: To evaluate the efficacy of intravitreal aflibercept injection (IAI) for vitrectomized eyes with diabetic macular edema (DME) at two years. Methods: This is a prospective, non-comparative, multicenter observational study including diabetic patients with visual acuity between 20/400 to 20/40 due to DME, who have undergone vitrectomy at least 3 months before the first aflibercept injection. Treatment protocol included 5 monthly aflibercept injection followed by a ProReNata regimen during the first year. Participants were managed at clinicians' discretion using Treat and Extend or Observe and Plan regimen during the second year. Visual acuity, OCT findings and number of IAI were assessed at two years. Results: Available data for 28 eyes with DME previously vitrectomized treated with aflibercept intravitreal injection during at least 2 years were collected. Visual gain was +5.4 letters (p = 0.01), and central macular thickness decreased significantly -62µm, p < 0.001) at 2 years. Resolution of macular edema allowing discontinuation of aflibercept was observed in 7 eyes (15%). Mean number of injections was 14.6, and mean interval injection was 6.4 weeks for 2 years. Conclusion: These results suggest that IAI is beneficial in vitrectomized eyes leading to improvement of visual and anatomical outcome which was maintained for 2 years.

EFFICACY AND SAFETY OF AFLIBERCEPT FOR THE TREATMENT OF IDIOPATHIC CHOROIDAL NEOVASCULARIZATION IN YOUNG PATIENTS: The INTUITION Study.

PURPOSE: To evaluate the mean change in visual acuity at 52 weeks in patients with idiopathic choroidal neovascularization treated with aflibercept. METHODS: We conducted a prospective noncomparative open-label Phase-II trial. The dosage regimen evaluated in this study was structured into two periods: (1) from inclusion to 20 weeks: a treat-and-extend period composed of three mandatory intravitreal injections, and complementary intravitreal injections performed if needed; (2) from 21 weeks to 52 weeks: a pro re nata period composed of intravitreal injections performed only if needed. RESULTS: A total of 19 patients were included, and 16 completed the 52-week study. At baseline, the mean best corrected visual acuity was 66.56 (±20.72) letters (≈20/50 Snellen equivalent), and the mean central retinal thickness was 376.74 µm (±93.77). At 52 weeks, the mean change in the best-corrected visual acuity was +19.50 (±19.36) letters [95% confidence interval = +9.18 to +29.82]. None of the patients included lost ≥15 letters at 24 weeks or 52 weeks. The mean change in central retinal thickness was -96.78 µm (±104.29) at 24 weeks and -86.22 µm (±112.27) at 52 weeks. The mean number of intravitreal injections was 5.4 (±3.0) at 52-weeks. No ocular serious adverse events related to the treatment were reported. CONCLUSION: The present analysis shows clinically significant functional and anatomical treatment effect of aflibercept in case of idiopathic choroidal neovascularization. The treat-and-extend regimen proposed after the first injection seems adequate to treat most neovessels.

One-Year Outcome of Aflibercept Intravitreal Injection in Vitrectomized Eyes with Diabetic Macular Edema.

AIM: To evaluate the efficacy of intravitreal Aflibercept injection (IAI) for vitrectomized eyes with diabetic macular edema (DME) at one year. METHODS: This is a prospective, non-comparative, multicenter observational study including diabetic patients whose HbA1c is < 9%, with visual acuity between 20/400 to 20/40 due to DME, who have undergone vitrectomy since at least 3 months before the first aflibercept injection. Treatment protocol included 5 monthly aflibercept injection followed by a ProReNata regimen during the first year. Visual acuity, OCT findings and number of IAI were assessed at 6 months and one year. RESULTS: Forty-six eyes were included. Indications for vitrectomy were epiretinal membrane (58.7%), intravitreal hemorrhage (26.1%), and vitreomacular traction (8.7%), retinal detachment (4.3%), and other cause (4.3%). Median duration of macular edema was 3 years. Median interval between vitrectomy and first visit was 9 months. Thirty eyes were non-naïve and received previously thermal laser (44.3%), intravitreal injection of triamcinolone (26.7%), of ranibizumab (70%), of dexamethasone implant (36.7%), or bevacizumab (6.7%). Data was available for 35 eyes at 1 year. Visual gain was significant, +6 letters (p <0.001) and central subfield thickness (CST) decreased significantly (-108µm, p < 0.001) at 1 year. Mean number of injections was 9.3 and mean interval injection was 5.8 weeks. CONCLUSION: These results suggest that IAI may be beneficial in vitrectomized eyes with refractory DME which require frequent injections to obtain visual and anatomical improvement. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov, registration Number NCT02874859.

Visual Acuity Gain Profiles and Anatomical Prognosis Factors in Patients with Drug-Naive Diabetic Macular Edema Treated with Dexamethasone Implant: The NAVEDEX Study.

The purpose of this study is to evaluate the visual acuity (VA) gain profiles between patients with drug-naive diabetic macular edema (DME) treated by dexamethasone implant (DEX-implant) and assess the baseline anatomical and functional factors that could influence the response to the treatment in real-life conditions. A retrospective, multi-center observational study included 129 eyes with drug-naive DME treated by DEX-implant. The Median follow-up was 13 months. Two groups of VA gain trajectories were identified-Group A, with 71% (n = 96) of patients whose average VA gain was less than five letters and Group B, with 29% (n = 33) of patients with an average gain of 20 letters. The probability of belonging to Group B was significantly higher in patients with baseline VA < 37 letters (p = 0.001). Ellipsoid zone alterations (EZAs) or disorganization of retinal inner layers (DRILs) were associated with a lower final VA (53.0 letters versus 66.4, p = 0.002) but without a significant difference in VA gain (4.9 letters versus 6.8, p = 0.582). Despite a low baseline VA, this subgroup of patients tends to have greater visual gain, encouraging treatment with DEX-implant in such advanced-stage disease. However, some baseline anatomic parameters, such as the presence of EZAs or DRILs, negatively influenced final vision.

Ophthalmic Artery and Superior Ophthalmic Vein Blood Flow Dynamics in Glaucoma Investigated by Phase Contrast Magnetic Resonance Imaging.

PRECIS: Ophthalmic artery (OA) and superior ophthalmic vein (SOV) blood flow were quantified by phase contrast magnetic resonance imaging (PC MRI) and seemed lower in glaucoma. Venous flow dynamics was different in glaucoma patients with a significantly decreased pulsatility. INTRODUCTION: Studies using color Doppler imaging and optical coherence tomography flowmetry strongly suggested that vascular changes are involved in the pathophysiology of glaucoma, but the venous outflow has been little studied beyond the episcleral veins. This study measured the OA and the SOV flow by PC MRI in glaucoma patients compared with controls. METHODS: Eleven primary open-angle glaucoma patients, with a mean±SD visual field deficit of -2.3±2.7 dB and retinal nerve fiber layer thickness of 92±13 µ, and 10 controls of similar age, were examined by PC MRI. The mean, maximal and minimal flow over cardiac cycle were measured. The variation of flow (ΔQ) was calculated. RESULTS: The OA mean±SD mean flow was 13.21±6.79 in patients and 15.09±7.62 mL/min in controls (P=0.35) and the OA maximal flow was 25.70±12.08 mL/min in patients, and 28.45±10.64 mL/min in controls (P=0.22). In the SOV the mean±SD mean flow was 6.46±5.50 mL/min in patients and 7.21±6.04 mL/min in controls (P=0.81) and the maximal flow was 9.06±6.67 in patients versus 11.96±9.29 mL/min in controls (P=0.47). The ΔQ in the SOV was significantly lower in patients (5.45±2.54 mL/min) than in controls (9.09±5.74 mL/min) (P=0.04). DISCUSSION: Although no significant difference was found, the mean and maximal flow in the OA and SOV seemed lower in glaucoma patients than in controls. The SOV flow waveform might be affected in glaucoma, corroborating the hypothesis of an impairment of venous outflow in those patients.

Visual prognosis of posterior and combined persistent fetal vasculature.

INTRODUCTION: The persistent fetal vasculature refers to congenital anomalies of the globe resulting from the abnormal persistence of the hyaloid vascular system. It can present as anterior, posterior, or combined form. The aim of this study was to report the visual outcomes of posterior and combined forms of persistent fetal vasculature. METHODS: This retrospective, single-center study included every patient referred to our outpatient clinic with a posterior or combined form of persistent fetal vasculature. The primary endpoint was the visual acuity of the impaired eye, or of the best eye if bilateral, at the end of follow-up. RESULTS: In total, 18 eyes of 14 patients (10 males) were included. The combined form was the most prevalent (12 of 18 eyes), and 4 of 14 patients had bilateral impairment. The range of assessed visual acuity was from 20/2000 to 20/25. The best visual acuity in patients having undergone a surgical procedure was 20/63 (cataract extraction = 3, combined phacovitrectomy = 1). In patients who had been treated for amblyopia with patching, without surgery, the best visual acuity measured was 20/100 (5 patients). Among patients who had neither surgery nor patching therapy, there was one 63-year-old patient with a 20/25 visual acuity; the other ones had a low visual acuity of less than 20/200. All included eyes presented with nystagmus, amblyopia, and/or strabismus at the end of follow-up. CONCLUSION: The posterior and combined forms of persistent fetal vasculature are of poor visual prognosis. The severe or occulting presentations require surgery to obtain the same visual outcomes as the moderate forms treated for amblyopia with patching therapy.

Clinical and surgical risk factors for consecutive exotropia.

INTRODUCTION:: Consecutive exotropia is one of the complications of esotropia surgery. Its prevalence is estimated at 4%-27%. The aim of this study was to identify the risk factors for consecutive exotropia in the aftermath of surgical treatment of esotropia. METHODS:: Seventy-four patients examined in our strabismus consultation for a consecutive exotropia from January 2010 to June 2016 were retrospectively included. The age of onset of esotropia, the presence of amblyopia, the age of esotropia surgery and chosen procedure, the refractive errors, the anomalies of ocular motility, the age of onset of the consecutive exotropia and its angle of deviation were reported. Statistical analyses were performed with Student's test and Fisher's exact test. RESULTS:: Esotropia occurred in 65% of cases before the age of 1 year, was associated with amblyopia in 51%, hyperopia in 55% or anisometropia in 31%. Surgery was performed before the age of 6 years for 55% of the patients and involved for 52% the both medial recti. The angle of deviation of consecutive exotropia was ≤20 prism dioptres (PD) in 39%, 21-40 PD in 39% and ≥ 40 PD in 22%, related to amblyopia (p = 0.028), and to high hypermetropia (p = 0.05). DISCUSSION:: Amblyopia and hyperopia were the most important risk factors of consecutive exotropia in our series. Early onset esotropia, stereopsis abnormalities, anisometropia, oblique dysfunction, convergence insufficiency appeared but did not reach statistical significance. CONCLUSION:: Amblyopia is a major risk factor that should be taken into consideration during surgery of an esotropia.

Quantification of blood flow in the superior ophthalmic vein using phase contrast magnetic resonance imaging.

Phase contrast magnetic resonance imaging (PC MRI), a validated, non-invasive technique for measuring intracranial blood and cerebrospinal flows, has been recently applied to studies of blood flow of the ophthalmic artery (OA). This study evaluated PC-MRI's ability to quantify blood flow in the superior ophthalmic vein (SOV). We analyzed with 3 T PC MRI the blood flow in the SOV in 11 healthy subjects and, for comparison purpose, in the OA. Segmentation software was used to analyze the PC images and quantify the variation in blood flow over the cardiac cycle in each of the vessels. The anatomy of the orbital veins was also assessed. We were able to measure the blood flow in 19 SOV; the mean ±â€¯standard deviation (SD) SOV flow was 9.13 ±â€¯7.10 mL/min with a mean ±â€¯SD variation of flow during cardiac cycle of 8.45 ±â€¯4.90 mL/min. The mean ±â€¯SD flow in the OA was 12.83 ±â€¯8.36 mL/min. The SOV was constantly present, with a mean cross-sectional area of 2.43 mm2. A medium and an inferior ophthalmic veins were found in 5 and 3 orbits, respectively. In conclusion, PC MRI is able to measure SOV as well as OA flows. To the best of our knowledge, the present study is the first to provide quantitative SOV blood flow values using PC MRI. Investigations of hydrocephalus, intracranial hypertension and even glaucoma might be facilitated by the application of this quantitative imaging modality.

Dietary, environmental, and genetic risk factors of Extensive Macular Atrophy with Pseudodrusen, a severe bilateral macular atrophy of middle-aged patients.

EMAP (Extensive Macular Atrophy with Pseudodrusen) is a maculopathy we recently described that shares pseudodrusen and geographic atrophy with Age-related Macular Disease (AMD). EMAP differs from AMD by an earlier age of onset (50-55 years) and a characteristic natural history comprising a night blindness followed by a severe visual loss. In a prospective case-control study, ten referral centers included 115 EMAP (70 women, 45 men) patients and 345 matched controls to appraise dietary, environmental, and genetic risk factors. The incidence of EMAP (mean 2.95/1.106) was lower in Provence-Côte d'Azur with a Mediterranean diet (1.9/1.106), and higher in regions with intensive farming or industrialized activities (5 to 20/1.106). EMAP patients reported toxic exposure during professional activities (OR 2.29). The frequencies of common AMD complement factor risk alleles were comparable in EMAP. By contrast, only one EMAP patient had a rare AMD variant. This study suggests that EMAP could be a neurodegenerative disorder caused by lifelong toxic exposure and that it is associated with a chronic inflammation and abnormal complement pathway regulation. This leads to diffuse subretinal deposits with rod dysfunction and cone apoptosis around the age of 50 with characteristic extensive macular atrophy and paving stones in the far peripheral retina.

Clostridium perfringens panophthalmitis and orbital cellulitis: a case report.

BACKGROUND: Clostridium perfringens is an uncommon pathogen in endophthalmitis, causing rapid destruction of ocular tissues. Clostridium perfringens infection typically occurs after penetrating injury with soil-contaminated foreign bodies. CASE REPORT: Here, we describe the case of a 17-year-old male who sustained a penetrating injury with a metallic intraocular foreign body and who rapidly developed severe C. perfringens panophthalmitis with orbital cellulitis. He was managed by systemic and intravitreal antibiotics, resulting in preservation of the globe, but a poor visual outcome. CONCLUSION: Clostridial endophthalmitis secondary to penetrating injuries is a fulminant infection, almost always resulting in loss of the globe in the case of advanced infection. When feasible, early vitrectomy and intravitreal antibiotics should be considered in patients with penetrating eye injuries with contaminated foreign bodies.

Effectiveness and safety of dexamethasone implants for postsurgical macular oedema including Irvine-Gass syndrome: the EPISODIC-2 study.

AIM: To assess the effectiveness of intravitreal dexamethasone implants for treating postsurgical macular oedema (PSMO) including Irvine-Gass syndrome and determining the predictive factors of treatment response. METHODS: Descriptive, observational, retrospective, consecutive, uncontrolled, multicentre, national case series. One hundred patients were included between April 2011 and June 2014, with a minimum of 1-year follow-up. Patients received dexamethasone implant 0.7 mg at baseline. Clinical characteristics, best-corrected visual acuity (BCVA), central subfield macular thickness (CSMT) and intraocular pressure were measured at each visit. The main outcome measure was the change in BCVA (Early Treatment of Diabetic Retinopathy Study (ETDRS) letters: L). An analysis of predictive factors of treatment response is also provided. RESULTS: Mean improvement in BCVA was 9.6 (±10.6) L at month 6 and 10.3 (±10.7) L at month 12 (p<0.001). The proportion of eyes with gains in BCVA of 15 or more letters was 32.5% and 37.5% at months 6 and 12, respectively. The mean reduction in CSMT was 135.2 and 160.9 µm at months 6 and 12, respectively (p<0.001). Thirty-seven per cent of patients did not need a second injection after the first injection during follow-up. The presence of at least one PSMO risk factor decreases the probability of a gain in visual acuity (VA) ≥10 L (p=0.006). Initial VA ≤50 L at baseline and non-naïve status decrease the probability of having only one injection during follow-up (p=0.044). CONCLUSIONS: The significant gain in BCVA from baseline achieved at month 6 was maintained at month 12 after intravitreal injection of dexamethasone implant. Naïve status seems to be a good predictive factor of treatment response.

Ocular blood flow and cerebrospinal fluid pressure in glaucoma.

Disease mechanism underlying glaucoma remains unclear. Extensive research on this pathology has highlighted changes in vascular parameters and in circulation of the cerebrospinal fluid (CSF). Here, we review the most recent research on alterations in ocular blood flow and/or CSF flow in glaucoma. Ultrasound Doppler imaging studies have shown an increased resistive index in ophthalmic artery's in glaucoma. Furthermore, changes in optic nerve CSF circulation, which can be assessed with magnetic resonance imaging, may lead to a greater translaminar pressure difference, mechanical stress, and poor clearance of toxic substances. This constitutes a new approach for understanding blood-CSF interactions involved in glaucoma.

Early-onset hypoparathyroidism and chronic keratitis revealing APECED.

Early diagnosis of potentially life-threatening autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is crucial, but is often delayed due to the clinical heterogeneity of the disorder. Even in the absence of the classic disease triad of chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenocortical insufficiency, a diagnosis of APECED should be considered in children who have hypoparathyroidism and chronic keratitis, with a past medical history showing a mild and transient Candida infection.

Effectiveness and safety of dexamethasone implants for post-surgical macular oedema including Irvine-Gass syndrome: the EPISODIC study.

AIM: To assess the effectiveness and safety of intravitreal dexamethasone implants for treating post-surgical macular oedema, including Irvine-Gass syndrome refractory to first-line treatments. METHODS: Descriptive, observational, retrospective, consecutive, uncontrolled, multicentre, national case series. 50 patients were included in the study between March 2011 and June 2013 with a minimum 6 months follow-up. At baseline, each patient received a dexamethasone implant 0.7 mg (Ozurdex). Best-corrected visual acuity (BCVA), central subfield macular thickness (CSMT), and intraocular pressure (IOP) were measured at baseline and then monthly. The main outcome measure was the mean change in BCVA (in ETDRS letters (Early Treatment Diabetic Retinopathy Study): L) RESULTS: Baseline mean±SD BCVA was 55.7±15.4 L. At month 2, BCVA was 71.8±10.5 L and 61.2% of patients had an increase of more than 15 letters. Baseline mean CSMT was 544±117.2 µm and this decreased to 302 µm at month 2. Anatomic and functional recurrences were both first detected from month 3 and continued throughout follow-up, with values consistently above baseline. The peak in IOP was reached in month 1 with mean IOP of 15.3±4.6 mm Hg. Of the 39/50 patients followed up for 12 months, 49% received a second injection. The anatomic and functional response and safety patterns were similar to that obtained with the first intravitreal injection, demonstrating Ozurdex's reproducibility. However, more than half of the patients followed-up for at least 1 year presented neither functional nor anatomical recurrence. CONCLUSIONS: Ozurdex would appear to be an interesting alternative therapy for treating post-surgical macular oedema, including Irvine-Gass syndrome refractory to first-line treatments.

Unusual acute endophthalmitis due to an as yet unclassified Acinetobacter gyllenbergii-like isolate.

We report a case of postoperative endophthalmitis due to an as yet unclassified Acinetobacter gyllenbergii-like isolate. The functional outcome was rapidly negative despite antibacterial therapy. This novel species, which cannot be identified by classical biochemical methods, may represent an underestimated opportunistic pathogen responsible for acute pyogenic infections.

Visual development in infants: physiological and pathological mechanisms.

PURPOSE OF REVIEW: This review summarizes current knowledge on ocular conditions related to abnormal visual development in infants, including prevalence, risk factors, causes, and mechanisms involved. We discuss the role of eyeball growth with pathologic mechanism of visual deprivation and development of amblyopia in infants, particular developmental issues in preterm neonates, methods of visual assessment and screening, diagnosis, treatment, and nutritional issues. RECENT FINDINGS: Visual development is incomplete at birth, particularly in premature infants; maturation of the visual system--including neurological and ocular components--is influenced by many factors including prenatal and postnatal nutrition and postnatal visual stimulation. In early life, particularly during sensitive periods of development, abnormal visual input, for example caused by visual deprivation mechanism, amblyopia, or ocular misalignment, leads to abnormalities in visual development, including abnormal eyeball growth and neurological changes. Untreated anomalies or abnormal visual development can result in long-term or even permanent visual impairment. Nutrition plays a key role in visual development: infant formulas containing nutrients essential for normal visual development (specifically omega-3 fatty acid docosahexaenoic acid and omega-6 fatty acid arachidonic acid) may protect nonbreast-fed infants against visual development abnormalities. SUMMARY: Problems related to visual anomalies are common among young children, particularly in preterm neonates. Screening to enable early diagnosis and correction of visual deficiency is important as abnormal visual input can lead to abnormalities in visual development, which can become permanent visual impairment if left untreated. Optimized nutrition can help to reduce the risk of abnormal visual development and prevent long-term or permanent visual deficits.

Ocular complications of atopic dermatitis in children.

Ocular complications of atopic dermatitis in adults are blepharitis, keratoconjunctivitis, keratoconus, uveitis, subcapsular cataract and retinal detachment. Their frequency varies from 25% to 50%. The aim of this study was to assess the frequency and type of ophthalmological complications in children with atopic dermatitis. The secondary objectives of the study were to determine whether there is a correlation between severity of atopic dermatitis, face involvement, external ocular signs and the presence of ocular complications, and to identify risk factors for ophthalmological complications. Thirty-seven boys and 22 girls, mean age 36.2 months, with atopic dermatitis were examined. Atopic dermatitis severity was mild according to the SCORAD index (31.6 +/- 17.0). Fifteen (25.4%) children had external ocular signs, one had a nuclear cataract, 11 had benign papillofollicular conjunctivitis, one had purulent bacterial conjunctivitis, one had chronic atopic blepharitis and one had amblyopia. Severity of atopic dermatitis, face involvement, and external ocular signs did not seem to influence the incidence of ocular involvement. This study suggests that severe ocular complications are rare in young children with mild atopic dermatitis.