Importance
Long‐term data of intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors are lacking.
Background
This study aims to assess visual and anatomic outcomes of eyes ...with neovascular age‐related macular degeneration (nAMD) after 10 years of anti‐VEGF therapy.
Design
Retrospective analysis of data from a prospectively designed database.
Participants
One hundred and sixteen eyes with nAMD (94 participants) that started anti‐VEGF therapy at least 10 years earlier.
Methods
Eyes were tracked by the Fight Retinal Blindness! registry.
Main Outcome Measures
Mean change in visual acuity at 10 years vs baseline. Visual acuity was assessed by the number of letters read on a logarithm of the minimum angle of resolution chart.
Results
Eyes received a median of 27.5 injections over 10 years. Mean visual acuity was 57.5 letters (SD 17.5) at baseline. It increased slightly at 1 year, then dropped steadily by 18 letters (95% CI: 13.7; 22.3) at 10 years. Overall, 10% of eyes gained ≥10 letters, 64% lost ≥10 letters and 23% remained stable (±5 letters from baseline). Geographic atrophy and subretinal fibrosis were found in 93% and 71%, respectively, after 10 years, both mostly affecting the centre of the fovea. Pre‐treated eyes (47.5%) had significantly worse visual acuity than treatment‐naïve eyes at baseline and during follow‐up and were significantly more likely to have atrophy and fibrosis.
Conclusions and Relevance
Despite short‐term stabilization, long‐term visual outcomes of nAMD eyes under anti‐VEGF therapy may be poor. Development of atrophy and fibrosis, resulting from the natural progression of the disease, may partly explain this evolution.
To evaluate the relative efficacy and safety profile of bevacizumab versus ranibizumab intravitreal injections for the treatment of neovascular age-related macular degeneration (AMD).
Multicenter, ...prospective, noninferiority, double-masked, randomized clinical trial performed in 38 French ophthalmology centers. The noninferiority limit was 5 letters.
Patients aged ≥50 years were eligible if they presented with subfoveal neovascular AMD, with best-corrected visual acuity (BVCA) in the study eye of between 20/32 and 20/320 measured on the Early Treatment of Diabetic Retinopathy Study chart and a lesion area of less than 12 optic disc areas (DA).
Patients were randomly assigned to intravitreal administration of bevacizumab (1.25 mg) or ranibizumab (0.50 mg). Hospital pharmacies were responsible for preparing, blinding, and dispensing treatments. Patients were followed for 1 year, with a loading dose of 3 monthly intravitreal injections, followed by an as-needed regimen (1 injection in case of active disease) for the remaining 9 months with monthly follow-up.
Mean change in visual acuity at 1 year.
Between June 2009 and November 2011, 501 patients were randomized. In the per protocol analysis, bevacizumab was noninferior to ranibizumab (bevacizumab minus ranibizumab +1.89 letters; 95% confidence interval CI, -1.16 to +4.93, P < 0.0001). The intention-to-treat analysis was concordant. The mean number of injections was 6.8 in the bevacizumab group and 6.5 in the ranibizumab group (P = 0.39). Both drugs reduced the central subfield macular thickness, with a mean decrease of 95 μm for bevacizumab and 107 μm for ranibizumab (P = 0.27). There were no significant differences in the presence of subretinal or intraretinal fluid at final evaluation, dye leakage on angiogram, or change in choroidal neovascular area. The proportion of patients with serious adverse events was 12.6% in the bevacizumab group and 12.1% in the ranibizumab group (P = 0.88). The proportion of patients with serious systemic or ocular adverse events was similar in both groups.
Bevacizumab was noninferior to ranibizumab for visual acuity at 1 year with similar safety profiles. Ranibizumab tended to have a better anatomic outcome. The results are similar to those of previous head-to-head studies.
Purpose
To describe and interpret the features of pachychoroid neovasculopathy (PNV) using optical coherence tomography angiography (OCTA) technique.
Methods
This is an observational case series of ...patients who presented with PNV. Best‐corrected visual acuity (BCVA), anterior segment examination, dilated funduscopic examination, infrared and autofluorescence fundus images and spectral‐domain optical coherence tomography (SD‐OCT; B‐scan, ‘en‐face’ and OCTA) were carried out for all patients. Choroid thickness was measured using enhanced depth imaging (EDI) mode. Colour fundus photographs, fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were not performed systematically. Optical coherence tomography angiography (OCTA) features of PNV are described and interpreted.
Results
Five eyes of five patients with a mean age of 62.2 years (range, 53–73 years) presenting with PNV were analysed. They all presented pachychoroid pigment epitheliopathy (PPE) with choroidal thickening and dilated choroidal vessels as seen with EDI‐OCT. Fluorescein angiography (FFA) was performed in three patients showing multiple areas of retinal pigment epithelium atrophy and fundus lesions suggestive of chronic central serous chorioretinopathy. Indocyanine green angiography (ICGA) in one patient confirmed the presence of large choroidal veins and choroidal hyperpermeability seen beneath the area of the neovascular tissue. Two eyes had the appearance of polypoidal structures within the neovascular tissue, with the characteristic aspect of the polypoidal lesions on B‐scan and ‘en‐face’. Optical coherence tomography angiography (OCTA) showed the appearance of tangled filamentous vascular network in all eyes.
Conclusion
Optical coherence tomography angiography (OCTA) is a safe, highly sensitive and specific examination for the detection of type 1 neovascularization associated with PPE. Features are characteristic of tangled filamentous vessels overlying a focal area of thickened choroid.
Background and purpose
This study was undertaken to determine the role of optical coherence tomography (OCT) in predicting the final visual and structural outcome, and to evaluate the correlation ...between functional eye outcome and retinal changes, in patients with a first episode of optic neuritis (ON).
Methods
In this prospective study, consecutive adult patients with acute ON underwent ophthalmological evaluation at baseline and at 1 and 12 months, including OCT measurements of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell and inner plexiform layer, and inner nuclear layer thicknesses; high‐ and low‐contrast visual acuity; visual field assessment; and baseline brain magnetic resonance imaging. Univariate and multivariate linear regressions were used to assess predictive factors of outcome. Correlations between 12‐month visual function and retinal structure were estimated by Spearman coefficients. Two groups of patients were analyzed, with or without multiple sclerosis (MS).
Results
Among 116 patients, 79 (68.1%) had MS, and 37 (31.9%) had ON not related to MS (including 19 idiopathic i.e., isolated ON, and 13 and five with myelin oligodendrocyte glycoprotein and aquaporin‐4 antibodies, respectively). We found no independent predictive factor of visual and retinal outcome. Analysis of the relationship between the visual field test (mean deviation) and pRNFL thickness demonstrated a threshold of 75.4 μm and 66.4 μm, below which the mean deviation was worse, for patients with MS (p = 0.007) and without MS (p < 0.001), respectively.
Conclusions
We found that inner retinal layer measurements during the first month are not predictive of final outcome. The critical threshold of axonal integrity, below which visual function is damaged, is different between patients with and without MS.
The critical threshold of axonal integrity below which visual function is damaged after optic neuritis (ON) is different between patients with multiple sclerosis (MS) and those without MS. Thinning of the inner retinal layers significantly correlated with visual impairment (assessed by mean deviation MD on visual fields tests) at final assessment. We identified a threshold of 75.4 μm for peripapillary retinal nerve fiber layer (pRNFL) thickness in MS patients, below which the MD is significantly worse. However, in ON not related to MS, a tipping point of 66 μm was determined for pRNFL, below which the visual function deteriorates abruptly, reflecting different pathological processes in MS and non‐MS.
Background: Acute macular neuroretinopathy (AMN) is an increasingly diagnosed disorder associated with several diseases. The aim of this study was to report the incidence of AMN cases diagnosed ...during the 2020 coronavirus disease 2019 (COVID-19) pandemic year in a French hospital, and to describe their different forms. Methods: All patients diagnosed between 2019 and 2020, in Paris Rothschild Foundation Hospital, with AMN, paracentral acute middle maculopathy (PAMM) and multiple evanescent white dot syndrome (MEWDS) were retrospectively collected using the software Ophtalmoquery® (Corilus, V1.86.0018, 9050 Gand, Belgium). Systemic and ophthalmological data from AMN patients were analyzed. Results: Eleven patients were diagnosed with AMN in 2020 vs. only one patient reported in 2019. The incidence of AMN significantly increased from 0.66/100,000 visits in 2019 to 8.97/100,000 visits in 2020 (p = 0.001), whereas the incidence of PAMM and MEWDS remained unchanged. Four (36%) of these AMN patients were tested for COVID-19 and received positive polymerase chain reaction (PCR) tests. Conclusions: The incidence of AMN cases increased significantly in our institution in 2020, which was the year of the COVID-19 pandemic. All AMN-tested patients received a positive COVID PCR test, suggesting a possible causative link. According to the different clinical presentations, AMN may reflect different severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pathogenic mechanisms.
Purpose To 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). Design Phase I/II, open-label, multicenter, dose-escalation study. Methods Patients 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. Results Altogether, 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. Conclusions A 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.
To report the occurrence of paracentral acute middle maculopathy (PAMM) in giant cell arteritis (GCA), describe its features and outcomes, and identify risk factors associated with PAMM in patients ...with GCA.
Review of medical records of patients with GCA who were examined in the Rothschild Foundation Hospital. Patients were divided into three groups: GCA with PAMM (Group 1), GCA with ophthalmic involvement but without PAMM (Group 2), and GCA without ophthalmic involvement (Group 3). We analyzed the data for age, sex, medical history, laboratory testing, visual acuity, and posterior segment vascular involvement.
Among the 96 patients who met the inclusion criteria, 52 had ophthalmic involvement, and 16 patients were included in Group 1 (GCA with PAMM). In this subgroup, the mean age was 81.6 years and was found to be older than other groups. The visual prognosis was similar between Groups 1 and 2. Of the 20 eyes with PAMM, 35% were also associated with homolateral anterior ischemic optic neuropathy. No statistical difference was found in initial symptoms, signs, and laboratory testing.
Paracentral acute middle maculopathy is frequently observed lesions in ocular GCA. Patients can present with isolated findings of PAMM as the only indication of GCA. Optical coherence tomography of the macula should be routinely performed in patients with suspected GCA, specifically if they complain of visual changes, to look for signs of ischemia in the middle layers of the retina. Isolated PAMM should raise suspicion for GCA in patients at risk.
Purpose
Validation of a recently described central serous chorioretinopathy (CSCR) classification system and assessment of levels of agreement among 10 retina physicians.
Methods
This was a ...cross-sectional (inter-reader agreement) study. Ten retina physicians (assigned a role of masked grader) were provided with a comprehensive dataset of 61 eyes of 34 patients of presumed CSCR. Relevant clinical details and multimodal imaging (fundus autofluorescence, fluorescein and indocyanine green angiography, optical coherence tomography) of both involved and fellow eye were electronically shared. Later, only the fellow eye images were resent to understand the influence of affected eye on the grading of the fellow eye. Multiple inter-grader agreement using Fleiss Kappa was performed to determine the level of agreement among the 10 graders.
p
value of ≤ 0.05 was considered statistically significant.
Results
Sixty-one eyes of 34 patients were evaluated. There was moderate agreement for major criteria with Fleiss Kappa value of 0.50 (
p
< 0.0001) with a single outlier observer. After excluding that observer, the Fleiss Kappa value increased to 0.57 (
p
< 0.0001) with statistically significant
p
values among all categories, i.e., simple CSC (
κ
= 0.575), complex CSC (
κ
= 0.621), and no CSC (
κ
= 0.452). Overall, moderate to substantial agreement was noted among the subtypes (primary, recurrent, and resolved). The influence of the affected eye on fellow eye grading was studied. The global Fleiss Kappa coefficient (
κ
= 0.642,
p
< 0.0001) showed substantial agreement when observers were aware of the affected eye grading. However, without prior available information on the affected eye, the inter-grader agreement was significantly lower (global
κ
= 0.255,
p
< 0.0001).
Conclusion
A fair-moderate inter-grader agreement among the masked graders suggests a need for further refinement of this novel classification system. Disease grading should include both eyes as lack of information on affected eye has a bearing on fellow eye grading and inter-grader agreement as shown by a significant difference in global
κ
values.
To determine the loss of follow-up ratio and reasons during the COVID-19 lockdown in patients with retinal diseases treated by anti-vascular endothelial growth factor intravitreal injections and to ...report the visual outcome and rate of complications of these patients 1 year after the end of the lockdown.
This is a prospective descriptive cohort study (NCT04395859) conducted at the Rothschild Foundation Hospital - Paris between April 2020 and May 2021. Patients with retinal diseases treated by repeated intravitreal anti-VEGF injections (IVI) since before October 2019 were included. They filled-out a questionnaire and were followed up during a period of 1 year.
During the COVID-19 lockdown 198 eyes (82.5%) of 157 patients (82.6%) received their injections in a timely manner (group 1) while 42 eyes (17.5%) of 33 patients (17.4%) had their injections delayed or missed (group 2). No statistically significant difference was found between group 1 and group 2 when comparing the change of mean best corrected distance visual acuity (BCVA) between month 12 and inclusion (p = 0.6) and the rate of ocular complications. The most frequent reasons for missing scheduled injections are appointments cancellation by the hospital (12 patients, 36%), fear of virus exposure during transportation (7 patients, 21%) or at the hospital (5 patients, 15%). Eighty-four percent (130/157 patients) of patients who attended their appointment were satisfied by the protective measures used in the hospital.
COVID-19 lockdown did not seem to negatively affect the 1-year outcome of patients with retinal diseases treated by anti-VEGF IVIs who missed their scheduled injections. The BCVA and rate of complications at 1 year did not differ whether patients missed their scheduled injections or not. Maintaining IVIs during lockdown periods and educating patients about the risks of missing injections are pivotal in improving prognosis of retinal diseases.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Wilson's disease (WD) is an autosomal recessive genetic disorder due to a mutation of the ATP7B gene, resulting in impaired hepatic copper excretion and accumulation in various tissues. Ocular ...findings are one of the hallmarks of the disease. Many ophthalmological manifestations have been described and new techniques are currently available to improve their diagnosis and to follow their evolution. We have performed a systematic PubMed search to summarize available data of the recent literature on the most frequent ophthalmological disorders associated with WD, and to discuss the newest techniques used for their detection and follow-up during treatment. In total, 49 articles were retained for this review. The most common ocular findings seen in WD patients are Kayser-Fleischer ring (KFR) and sunflower cataracts. Other ocular manifestations may involve retinal tissue, visual systems and eye mobility. Diagnosis and follow-up under decoppering treatment of these ocular findings are generally easily performed with slit-lamp examination (SLE). However, new techniques are available for the precocious detection of ocular findings due to WD and may be of great value for non-experimented ophthalmologists and non-ophthalmologists practitioners. Among those techniques, anterior segment optical coherence tomography (AS-OCT) and Scheimpflug imaging are discussed.
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