Search

Objective: To describe the management of diabetic macular oedema (DME) patients from the entire French population between 2012 and 2018., Methods: In this retrospective longitudinal study, we identified adults treated for DME from the French population using the exhaustive French National Health Information database (SNDS), and an algorithm based on diagnosis and procedure codes, and reimbursed treatments., Results: Between 2012 and 2018, we identified 53 584 treated DME patients, who were followed for up to 7 years from DME treatment initiation. Optical coherence tomography (OCT) became the predominant imaging tool to diagnose DME. Only 14% of patients consulted a diabetologist or endocrinologist in the 3 months prior to initiating DME treatment, whereas 84% consulted a general practitioner. The percentage of patients consulting an ophthalmologist declined over time, from 97% of patients in Year 1 (median of 9 consultations), to 46% in Year 7 (median of 7 consultations). The median DME treatment duration with an anti-VEGF and/or dexamethasone implant treatment was 9 months; 54% of patients had a treatment duration less than 1 year. First-line treatment was more common with ranibizumab (55% of patients) than with aflibercept (30%), or dexamethasone implant (15%). About 25% of patients who initiated anti-VEGF treatment switched treatment at least once, while 30% of patients who initiated dexamethasone implant switched to anti-VEGF treatment at least once., Conclusions: French DME patients seem well-monitored by their ophthalmologist, but median DME treatment duration was just 9 months. These results emphasise the challenge to manage and treat patients with DME over the long term., (© 2023 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Macular edema (ME) results from hyperpermeability of retinal vessels, leading to chronic extravasation of plasma components into the retina and hence potentially severe visual acuity loss. Current standard of care consists in using intravitreal injections (IVI), which results in a significant medical and economic burden. During diabetic retinopathy (DR) or retinal vein occlusion (RVO), it has recently been shown that focal vascular anomalies (capillary macro-aneurysms, also termed TelCaps) for telangiectatic capillaries may play a central role in the onset, early recurrence, and/or persistence of ME. Since targeted photocoagulation of TelCaps may improve vision, identification, and photocoagulation of TelCaps, it may represent a way to improve management of ME., Objective: The Targeted Laser in (Diabetic) Macular Edema (TalaDME) study aims to evaluate whether ICG-guided targeted laser (IGTL), in association with standard of care by IVI, allows reducing the number of injections during the first year of treatment compared with IVI only, while remaining non-inferior for visual acuity., Methods: TalaDME is a French, multicentric, two-arms, randomized, sham laser-controlled, double-masked trial evaluating the effect of photocoagulation of TelCaps combined to IVI in patients with ME associated with TelCaps. Patients with vision loss related to center involved ME secondary to RVO or DR and presenting TelCaps are eligible. Two hundred and seventy eyes of 270 patients are randomized in a 1:1 ratio to standard care, i.e., IVI of anti-VEGF solely (control group) or combined with IGTL therapy (experimental group). Stratification is done on the cause of ME (i.e., RVO versus diabetes). Anti-VEGF IVI are administered to both groups monthly for 3 months (loading dose) and then with a pro re nata regimen with a monthly follow-up for 12 months. The primary endpoint will be the number of IVI and the change in visual acuity from baseline to 12 months. Secondary endpoints will be the changes in central macular thickness, impact on quality of life, cost of treatment, and incremental cost-utility ratio in each groups., Key Safety: Rare but severe AE linked to the use of IVI and laser, and previously described, are expected. In the sham group, rescue laser photocoagulation may be administered by the unmasked investigator if deemed necessary at month 3., Discussion: The best management of ME associated with TelCaps is debated, and there have been no randomized study designed to answer this question. Given the fact that TelCaps may affect 30 to 60% of patients with chronic ME due to DR or RVO, a large number of patients could benefit from a specific management of TelCaps. TalaDME aims to establish the clinical and medico-economic benefits of additional targeted laser. The results of TalaDME may raise new recommendations for managing ME and impact healthcare costs., Trial Registration: EudraCT: 2018-A00800-55/ NCT03751501. Registration date: Nov. 23, 2018., (© 2024. The Author(s).)

Introduction: The aim of this study was to describe the management of neovascular age-related macular degeneration (nAMD) in French patients between 2008 and 2018., Methods: This was a retrospective longitudinal cohort study using exhaustive nationwide health records from the French National Health Information database. Enrollment criteria were adults aged ≥ 50 years, nAMD diagnosis, or reimbursement for nAMD treatments (anti-vascular epithelial growth factor [VEGF] injection or dynamic phototherapy with verteporfin). Exclusion criteria were high myopia, diagnosis of other retinal diseases, and treatments for other macular diseases (dexamethasone implant, laser). Main outcome measures were consumption of medical care and nAMD treatments per calendar year and number of years of follow-up., Results: Between 2008 and 2018, we identified 342,961 patients who have been treated for nAMD. Median duration of ophthalmological follow-up exceeded 7 years (90 months). The median annual number of ophthalmology consultations decreased from nine visits in year 1 after treatment initiation to four visits from year 7 onwards. The median duration of nAMD treatment was 10.1 months for all patients, with 48.5% of patients undergoing treatment for < 1 year. Only 24.4% of patients had maintained treatment at year 11. Patients remaining under treatment had a median of four anti-VEGF treatments per year throughout the 10-year study period. Ranibizumab was the more common first-line treatment (67.5% of patients) compared to aflibercept (32.4%). About 20% of patients who initiated treatment switched treatment at least once., Conclusions: LANDSCAPE provides exhaustive nationwide data on the real-world management of nAMD in France over a 10-year period. Further investigation into short treatment duration is required, especially in terms of understanding its relation to visual outcomes., (© 2023. The Author(s).)

Purpose: Posterior uveitis is a common chorioretinal pathology affecting all ages worldwide and is a frequent reason for referral to the retina clinic. The spectrum of etiologies for uveitis is very broad and includes infectious and auto-immune diseases. Inflammation can be confined to the eye or may be a part of systemic disease. A useful outline is therefore proposed to aid in the correct diagnosis of these challenging entities. The situation is further complicated by the fact that many neoplastic conditions resemble features of posterior uveitis; they are known as "masqueraders of uveitis". Here, we summarize different posterior uveitides that present with rare findings, along with masqueraders that can be difficult to distinguish. These conditions pose a diagnostic dilemma resulting in delay in treatment because of diagnostic uncertainty., Methods: An extensive literature search was performed on the MEDLINE/PUBMED, EBSCO and Cochrane CENTRAL databases from January 1985 to January 2022 for original studies and reviews of predetermined diagnoses that include posterior uveitic entities, panuveitis and masquerade syndromes., Results: We described conditions that can present as mimickers of posterior uveitis (i.e., immune check-points inhibitors and Vogt-Koyanagi-Harada-like uveitis; leukemia and lymphoma associated posterior uveitis), inflammatory conditions that present as mimickers of retinal diseases (i.e., Purtscher-like retinopathy as a presentation of systemic lupus erythematosus; central serous chorioretinopathy masquerading inflammatory exudative retinal detachment), and uveitic conditions with rare and diagnostically challenging etiologies (i.e., paradoxical inflammatory effects of anti-TNF-α; post vaccination uveitis; ocular inflammation after intravitreal injection of antiangiogenic drugs)., Conclusion: This review of unique posterior uveitis cases highlights the overlapping features of posterior uveitis (paradoxical inflammatory effects of anti -TNF α and uveitis; Purtscher-like retinopathy as a presentation of systemic lupus erythematosus, …) and the nature of retinal conditions (ischemic ocular syndrome, or central retinal vein occlusion, amyloidosis, inherited conditions like retinitis pigmentosa, autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), etc.…) that may mimic them is represented. Careful review of past uveitis history, current medications and recent vaccinations, detailed examination of signs of past or present inflammation, eventually genetic testing and/ or multimodal retinal imaging (like fluorescein angiography, EDI-OCT, OCT-angiography for lupus Purtscher-like retinopathy evaluation, or ICG for central serous retinopathy, or retinal amyloid angiopathy) may aid in correct diagnosis., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To report an atypical case of MOG antibody-associated optic neuritis with Roth spots and widespread retinal hemorrhages., Case Report: A 49-year-old woman complained of 1 week history painful visual loss in the left eye. Funduscopy exam showed a severe optic disc edema associated with multiple peripapillar hemorrhages, peripheral retinal hemorrhages and Roth spots in the left eye. Orbit MRI revealed an hyperintensity in the left optic nerve, enhanced with gadolinium. The serum Myelin Oligodendrocyte (MOG) antibodies was found positive. Early intravenous high dose of steroids rapidly improved visual acuity and fundus abnormalities rapidly resolved., Conclusion: Retinal hemorrhages can also be detected in case of optic disc edema associated with an optic neuritis, as seen in MOGAD.

Introduction: Lenadogene nolparvovec is a promising novel gene therapy for patients with Leber hereditary optic neuropathy (LHON) carrying the m.11778G>A ND4 mutation (MT-ND4). A previous pooled analysis of phase 3 studies showed an improvement in visual acuity of patients injected with lenadogene nolparvovec compared to natural history. Here, we report updated results by incorporating data from the latest phase 3 trial REFLECT in the pool, increasing the number of treated patients from 76 to 174., Methods: The visual acuity of 174 MT-ND4-carrying patients with LHON injected in one or both eyes with lenadogene nolparvovec from four pooled phase 3 studies (REVERSE, RESCUE and their long-term extension trial RESTORE; and REFLECT trial) was compared to the spontaneous evolution of an external control group of 208 matched patients from 11 natural history studies., Results: Treated patients showed a clinically relevant and sustained improvement in their visual acuity when compared to natural history. Mean improvement versus natural history was - 0.30 logMAR (+ 15 ETDRS letters equivalent) at last observation (P < 0.01) with a maximal follow-up of 3.9 years after injection. Most treated eyes were on-chart as compared to less than half of natural history eyes at 48 months after vision loss (89.6% versus 48.1%; P < 0.01) and at last observation (76.1% versus 44.4%; P < 0.01). When we adjusted for covariates of interest (gender, age of onset, ethnicity, and duration of follow-up), the estimated mean gain was - 0.43 logMAR (+ 21.5 ETDRS letters equivalent) versus natural history at last observation (P < 0.0001). Treatment effect was consistent across all phase 3 clinical trials. Analyses from REFLECT suggest a larger treatment effect in patients receiving bilateral injection compared to unilateral injection., Conclusion: The efficacy of lenadogene nolparvovec in improving visual acuity in MT-ND4 LHON was confirmed in a large cohort of patients, compared to the spontaneous natural history decline. Bilateral injection of gene therapy may offer added benefits over unilateral injection., Trial Registration Numbers: NCT02652780 (REVERSE); NCT02652767 (RESCUE); NCT03406104 (RESTORE); NCT03293524 (REFLECT); NCT03295071 (REALITY)., (© 2022. The Author(s).)

Introduction: Information about real-world ranibizumab use is needed to optimize treatment of macular edema secondary to retinal vein occlusion (RVO). The BOREAL-RVO study assessed treatment use, effectiveness, and safety of 24-month treatment with ranibizumab 0.5 mg in patients with visual impairment due to macular edema secondary to RVO in a real-world setting., Methods: This was a multicenter, post-authorization, observational study in France, including patients starting ranibizumab for RVO. Primary endpoint was mean change from baseline in best-corrected visual acuity (BCVA) at month 6. Secondary endpoints were mean changes from baseline in BCVA at month 24 and central retinal thickness (CRT) at months 6 and 24, and treatment use in real-world setting., Results: 226 branch RVO (BRVO) and 196 central RVO (CRVO) patients were enrolled; 71.7% and 70.9% completed the 24-month follow-up, respectively. In BRVO, mean (SD) baseline BCVA was 55.2 (18.7) letters, with gains of 14.3 (13.7), 14.1 (16.5), 13.0 (17.5), and 11.4 (20.1) letters at months 3, 6, 12, and 24, respectively. In CRVO, mean (SD) baseline BCVA was 40.4 (25.6) letters, with gains of 16.0 (21.2), 9.5 (25.4), 9.2 (27.7), and 8.3 (23.8) letters at months 3, 6, 12, and 24, respectively. At month 24, 52% of BRVO and 41% of CRVO patients had gains of 15 or more letters. In BRVO, mean (SD) CRT values at baseline and months 3, 6, 12, and 24 were 550 (175), 315 (104), 343 (122), 335 (137), and 340 (105) μm. In CRVO, mean (SD) CRT values at baseline and months 3, 6, 12, and 24 were 643 (217), 327 (152), 400 (203), 379 (175), and 348 (161) μm. On average, BRVO patients had 3.8 injections for 6.9 visits by month 6, and 7.2 injections for 19.7 visits by month 24. CRVO patients had 2.7 injections for 4.2 visits by month 6 and 7.1 injections for 21.1 visits by month 24. Factors predictive of better BCVA gain at month 6 were age under 60 at baseline, lower baseline BCVA and BCVA gain at month 3. There were no new safety findings., Conclusion: Major improvements in BCVA and CRT were observed at month 3 after the induction phase and then were sustained up to month 24, with a slight decrease, probably due to under-treatment. This study demonstrated ranibizumab to be a safe and effective treatment for BRVO and CRVO in the real-world setting, although more regular or proactive treatment could further improve outcomes., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Aim: LANDSCAPE aimed to estimate the annual incidence and prevalence of treated diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) between 2008 and 2018., Methods: This French nationwide observational study used data from the French National Health Insurance Databases covering 99% of the French population. Data about healthcare consumption were used to identify adults treated with anti-VEGFs or dexamethasone implants (for DME) and with pan-retinal photocoagulation (for PDR). All French patients newly treated between 2008 and 2018 were included. Incidence and prevalence of treated DME and PDR were estimated for the age-matched general population and the population with diabetes in France. Sociodemographic characteristics and medical history were described in both populations., Results: We identified 53,584 treated DME patients and 127,273 treated PDR patients between 2008 and 2018, and 11,901 DME and 11,996 PDR new incident patients in 2018. The treated DME incidence in 2018 was 2.5 per 10,000 in the general population and 37.3 per 10,000 in the population with diabetes. Prevalence in 2018 was 9.5 and 143.7 per 10,000 in the respective populations. Treated PDR incidence in 2018 was 2.3 per 10,000 in the general population and 31.2 per 10,000 in the population with diabetes. Prevalence in 2018 was 19.9 and 270.3 per 10,000 in the respective populations. Incidence and prevalence were not age-dependent. Incidence of treated PDR incidence was relatively stable from 2008-2018. Incidence of treated DME incidence rose from 2012-2018, probably due to widening access to newly available treatments, such as anti-VEGFs., Conclusions: We provide exhaustive nationwide data on the incidence and prevalence of treated diabetic ocular complications in France over a 10-year period.

Purpose: This study aimed to estimate the incidence and prevalence of neovascular age-related macular degeneration (nAMD) in the French population between 2008 and 2018., Design: This was a retrospective, longitudinal population study using health care consumption data from the Système National des Données de Santé (SNDS; the French National Health Information Database), which covers approximately 99% of the French population., Participants: We identified individuals treated for nAMD from the French population 50 years of age and older. Identification criteria were nAMD diagnosis or reimbursement of nAMD treatments (anti-vascular endothelial growth factor intravitreal injection or dynamic phototherapy with verteporfin). Exclusion criteria were high myopia, diagnosis of other retinal diseases, and other treatments for macular diseases (dexamethasone implant, laser therapy, etc.)., Methods: We calculated incidence and prevalence based on the age-matched general population in France. Adjustment for age and sex was also performed for incidence., Main Outcome Measures: Incidence and prevalence of nAMD in the French population between 2008 and 2018., Results: Between 2008 and 2018, we identified 342 961 patients with nAMD (67.5% women). Mean ± standard deviation age at nAMD diagnosis or first treatment increased from 78.8 ± 8.1 years in 2008 to 81.2 ± 7.9 years in 2018. In 2018, annual incidence was 0.149% and prevalence was 1.062% for the French population 50 years of age or older. Incidence was stable over the 10-year period. Annual incidence increased with age (0.223%, 0.380%, and 0.603% in those 60 years of age or older, 70 years of age or older, and 80 years of age or older, respectively), with similar trends for prevalence. No major differences were observed among the 14 regions of France for incidence or prevalence. Neovascular age-related macular degeneration incidence in 2018 was not impacted by the availability of primary or ophthalmology care in patients' localities., Conclusions: The LANDSCAPE study provides exhaustive nationwide data on incidence and prevalence of nAMD in France over a 10-year period., (© 2022 by the American Academy of Ophthalmology.)

Objective: This work aimed to compare the evolution of visual outcomes in Leber hereditary optic neuropathy (LHON) patients treated with intravitreal gene therapy to the spontaneous evolution in prior natural history (NH) studies. Design: A combined analysis of two phase three randomized, double-masked, sham-controlled studies (REVERSE and RESCUE) and their joint long-term extension trial (CLIN06) evaluated the efficacy of rAAV2/2- ND4 vs. 11 pooled NH studies used as an external control. Subjects: The LHON subjects carried the m.11778G>A ND4 mutation and were aged ≥15 years at onset of vision loss. Methods: A total of 76 subjects received a single intravitreal rAAV2/2- ND4 injection in one eye and sham injection in the fellow eye within 1 year after vision loss in REVERSE and RESCUE. Both eyes were considered as treated due to the rAAV2/2- ND4 treatment efficacy observed in the contralateral eyes. Best corrected visual acuity (BCVA) from REVERSE, RESCUE, and CLIN06 up to 4.3 years after vision loss was compared to the visual acuity of 208 NH subjects matched for age and ND4 genotype. The NH subjects were from a LHON registry (REALITY) and from 10 NH studies. A locally estimated scatterplot smoothing (LOESS), non-parametric, local regression model was used to modelize visual acuity curves over time, and linear mixed model was used for statistical inferences. Main Outcome Measures: The main outcome measure was evolution of visual acuity from 12 months after vision loss, when REVERSE and RESCUE patients had been treated with rAAV2/2- ND4 . Results: The LOESS curves showed that the BCVA of the treated patients progressively improved from month 12 to 52 after vision loss. At month 48, there was a statistically and clinically relevant difference in visual acuity of -0.33 logarithm of the minimal angle of resolution (LogMAR) (16.5 ETDRS letters equivalent) in favor of treated eyes vs. NH eyes ( p < 0.01). Most treated eyes (88.7%) were on-chart at month 48 as compared to 48.1% of the NH eyes ( p < 0.01). The treatment effect at last observation remained statistically and clinically significant when adjusted for age and duration of follow-up (-0.32 LogMAR, p < 0.0001). Conclusions: The m.11778G>A LHON patients treated with rAAV2/2- ND4 exhibited an improvement of visual acuity over more than 4 years after vision loss to a degree not demonstrated in NH studies. Clinical Trial Registration: NCT02652767, NCT02652780, NCT03406104, and NCT03295071., Competing Interests: NN is a consultant for GenSight, Santhera Pharmaceuticals, and Stealth BioTherapeutics, has received research support from GenSight and Santhera Pharmaceuticals, has served on the Data Safety Monitoring Board for the Quark NAION study, and is a medical–legal consultant. PY-W-M is a consultant for GenSight and Stealth BioTherapeutics and has received research support from GenSight and Santhera Pharmaceuticals. VC is a consultant for Santhera Pharmaceuticals, GenSight, and Stealth BioTherapeutics and has received research support from Santhera Pharmaceuticals and Stealth BioTherapeutics. VB is a consultant for GenSight, Santhera Pharmaceuticals, and Stealth BioTherapeutics and has received research support from GenSight and Santhera Pharmaceuticals. MM is a consultant for GenSight Biologics and has received research support from GenSight. CV-C is a consultant for GenSight Biologics and Santhera Pharmaceuticals. RS is a consultant for GenSight Biologics. TK is a consultant for Santhera Pharmaceuticals, Chiesi, and GenSight Biologics and has received research support from Santhera Pharmaceuticals, GenSight Biologics, and Stealth BioTherapeutics. AS is a consultant for Stealth BioTherapeutics. CJ is an employee of eXYSTAT and a consultant for GenSight Biologics. FM is a co-founder of eXYSTAT and a consultant for GenSight Biologics. JS is a consultant for GenSight Biologics. MR and MT are GenSight Biologics employees. J-AS is a co-founder and shareholder of GenSight Biologics and a patent co-author on allotopic transport. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer GS declared a past co-authorship with two of the authors NN, VB the handling editor., (Copyright © 2021 Newman, Yu-Wai-Man, Carelli, Biousse, Moster, Vignal-Clermont, Sergott, Klopstock, Sadun, Girmens, La Morgia, DeBusk, Jurkute, Priglinger, Karanjia, Josse, Salzmann, Montestruc, Roux, Taiel and Sahel.)

Purpose: To evaluate the efficacy of a single intravitreal injection of rAAV2/2-ND4 in subjects with visual loss from Leber hereditary optic neuropathy (LHON)., Design: RESCUE is a multicenter, randomized, double-masked, sham-controlled, phase 3 clinical trial., Participants: Subjects with the m.11778G>A mitochondrial DNA mutation and vision loss ≤6 months from onset in 1 or both eyes were included., Methods: Each subject's right eye was randomly assigned (1:1) to treatment with rAAV2/2-ND4 (single injection of 9 × 10 10 viral genomes in 90 μl) or to sham injection. The left eye received the treatment not allocated to the right eye., Main Outcome Measures: The primary end point was the difference of the change from baseline in best-corrected visual acuity (BCVA) between rAAV2/2-ND4-treated and sham-treated eyes at week 48. Other outcome measures included contrast sensitivity, Humphrey visual field perimetry, retinal anatomic measures, and quality of life. Follow-up extended to week 96., Results: Efficacy analysis included 38 subjects. Mean age was 36.8 years, and 82% were male. Mean duration of vision loss at time of treatment was 3.6 months and 3.9 months in the rAAV2/2-ND4-treated eyes and sham-treated eyes, respectively. Mean baseline logarithm of the minimum angle of resolution (logMAR) BCVA (standard deviation) was 1.31 (0.52) in rAAV2/2-ND4-treated eyes and 1.26 (0.62) in sham-treated eyes, with a range from -0.20 to 2.51. At week 48, the difference of the change in BCVA from baseline between rAAV2/2-ND4-treated and sham-treated eyes was -0.01 logMAR (P = 0.89); the primary end point of a -0.3 logMAR (15-letter) difference was not met. The mean BCVA for both groups deteriorated over the initial weeks, reaching the worst levels at week 24, followed by a plateau phase until week 48, and then an improvement of +10 and +9 Early Treatment Diabetic Retinopathy Study letters equivalent from the plateau level in the rAAV2/2-ND4-treated and sham-treated eyes, respectively., Conclusions: At 96 weeks after unilateral injection of rAAV2/2-ND4, LHON subjects carrying the m.11778G>A mutation treated within 6 months after vision loss achieved comparable visual outcomes in the injected and uninjected eyes., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to evaluate the ability of a freely accessible internet algorithm to correctly identify the need for emergency ophthalmologic consultation for correct diagnosis and management., Method: This retrospective observational cohort study was based on the first 100 patients who requested recommendations on the necessity of breaking the lockdown for emergency ophthalmology consultation during the period from March to May 2020., Results: Ninety-one patients completed questionnaires. Forty-nine were directed to emergency consultation and 42 to differed scheduled visits or telemedicine visits. One patient sent for emergency consultation had an overestimated severity and could have been seen later, while two patients initially recommended for a scheduled visit were considered appropriate for emergency consultation. However, these patients' management did not suffer as a consequence of the delay. The sensitivity of the algorithm, defined as the number of emergency consultations suggested by the algorithm divided by the total number of emergency consultations deemed appropriate by the practitioner's final evaluation, was 96.0%. The specificity of the algorithm, defined as the number of patients recommended for delayed consultation by the algorithm divided by the number of patients deemed clinically appropriate for this approach, was 97.5%. The positive predictive value, defined as the number of appropriate emergency consultations divided by the total number of emergency consultations suggested by the algorithm, was 97.9%. Finally, the negative predictive value, defined as the number of appropriately deferred patients divided by the number of deferred patients recommended by the algorithm, was 95.2%., Conclusion: This study demonstrates the reliability of an algorithm based on patients' past medical history and symptoms to classify patients and direct them to either emergency consultation or to a more appropriate deferred, scheduled appointment. This algorithm might allow reduction of walk-in visits by half and thus help control patient flow into ophthalmologic emergency departments., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: Leber hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disease whose primary clinical manifestation is bilateral visual loss. Only a single therapy, idebenone, is approved in Europe for use in exceptional circumstances and no therapy is currently approved in the USA. LHON remains a disease with a high unmet medical need., Objective: This is a report of an open-label, single-center, dose-escalation study that evaluated the safety and tolerability of lenadogene nolparvovec in 15 subjects with LHON for up to 5 years following a single intravitreal injection at four dose levels., Methods: Subjects were enrolled sequentially in four cohorts followed by an additional cohort at the dose selected, and safety was assessed by an independent data safety monitoring board (DSMB) prior to any dose escalation., Results: Overall, the treatment was well tolerated during the 5-year follow-up. No serious adverse events were considered related to treatment, no unexpected adverse events occurred, and no grade 3 or 4 Common Terminology Criteria for Adverse Events were reported. Anterior chamber inflammation and vitritis were mostly managed with topical steroids, and ocular inflammation was considered to be dose limiting by the DSMB based on the benefits/risks for the subjects. Analysis of the logarithm of the minimal angle of resolution (LogMAR) visual acuity in both treated and untreated eyes showed clinically relevant and durable improvements compared with baseline. Mean improvements of - 0.44 and - 0.49 LogMAR for treated and untreated eyes, respectively, were noted, with a mean (± standard deviation) final value of LogMAR + 1.96 ± 0.60 and + 1.65 ± 0.34, respectively, at 5 years post-treatment administration. For the six subjects treated with the optimal dose level (9 × 10 10 viral genomes [vg]/eye), the mean visual acuity improvement from baseline reached - 0.68 LogMAR for treated eyes and - 0.64 LogMAR for untreated eyes, with a mean final value of LogMAR + 1.77 ± 0.52 and + 1.78 ± 0.34, respectively. While there was a meaningful improvement in visual acuity for REVEAL subjects, the final visual acuity was less favorable than that seen in the two subsequent pivotal phase III studies in which subjects were treated earlier during the course of their disease., Conclusion: Lenadogene nolparvovec was well tolerated with a good safety profile during 5 years of follow-up and may offer meaningful lasting improvements in vision for this LHON population., Clinical Trial Number: EUDRACT N° 2013-001405-90.

Purpose: To assess the efficacy, safety, and follow-up of 36-month treatment with ranibizumab in patients with diabetic macular edema (DME) in real-life setting., Methods: This is a prospective phase 4 observational study. Between December 2013 and April 2015, 84 ophthalmologists enrolled a total of 290 adult patients initiating ranibizumab for visual impairment due to DME and treated them according to their routine practice. The primary outcome (mean change in best-corrected visual acuity [BCVA] after 12 months) was previously reported. Here, we present outcomes after 36 months of follow-up for BCVA and change in central subfield thickness (CSFT) and report how participating ophthalmologists treated DME over a 3-year period (number of visits and injections and evolution of treatment strategy)., Results: Of the 290 patients enrolled, 187 (64.5%) completed the 36 months of the study (entire cohort). In the entire cohort, 97 patients were treated exclusively with ranibizumab throughout the study, and 90 patients switched to other intravitreal treatments. Mean BCVA was 64.2 (20.1) letters, representing a gain of +4.1 (19.9) letters from baseline to month 36 (M36). CSFT improved over the study, and by M36 had decreased by 127 (138) µm compared to baseline. Over the 36 months of follow-up, patients in the entire cohort paid their ophthalmologists a mean of 30.9 (12.2) visits and had a mean of 7.6 (5.2) any injections. Results for quality of life questionnaires NEI-VFQ25 and HUI-3 remained stable throughout the study. Multivariate analysis on the 145 patients with evaluable BCVA data at M36 found that male gender and milder baseline DME characteristics (BCVA ≥59 and CSFT <500 µm) were predictive factors for achieving a BCVA of ≥70 letters at M36. This study did not find any new safety signals, compared to the known profile of ranibizumab., Conclusions: Gains in BCVA in this real-life study were lower than those observed in randomized clinical trials with ranibizumab, mainly due to undertreatment. Safety analysis of ranibizumab did not yield any new safety concerns., (© 2020 S. Karger AG, Basel.)

A minor haplotype of the 10q26 locus conveys the strongest genetic risk for age-related macular degeneration (AMD). Here, we examined the mechanisms underlying this susceptibility. We found that monocytes from homozygous carriers of the 10q26 AMD-risk haplotype expressed high amounts of the serine peptidase HTRA1, and HTRA1 located to mononuclear phagocytes (MPs) in eyes of non-carriers with AMD. HTRA1 induced the persistence of monocytes in the subretinal space and exacerbated pathogenic inflammation by hydrolyzing thrombospondin 1 (TSP1), which separated the two CD47-binding sites within TSP1 that are necessary for efficient CD47 activation. This HTRA1-induced inhibition of CD47 signaling induced the expression of pro-inflammatory osteopontin (OPN). OPN expression increased in early monocyte-derived macrophages in 10q26 risk carriers. In models of subretinal inflammation and AMD, OPN deletion or pharmacological inhibition reversed HTRA1-induced pathogenic MP persistence. Our findings argue for the therapeutic potential of CD47 agonists and OPN inhibitors for the treatment of AMD., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: The purpose of this study (Tilak Study No: TIL-001) was to evaluate the medical modules on the mobile medical application OdySight and compare them to the gold standard tests for visual acuity, contrast sensitivity, and Amsler Grid., Methods: A total of 120 eyes were evaluated in an open-label, single-arm, prospective, single-site study during which participants performed monocular, gold standard tests for measuring visual acuity (Sloan Early Treatment Diabetic Retinopathy Study [ETDRS] letter chart at 40 cm testing distance and ETDRS letter chart at 4 m testing distance [40-cm and 4-m ETDRS, respectively), contrast sensitivity (Pelli-Robson contrast sensitivity chart [Pelli-Robson test]), and metamorphopsia/scotoma (Amsler Grid) followed by the respective modules on OdySight (also monocular). During this study, both the distance between the device and the patient's eye and room illumination were controlled by the examiner., Results: A Bland-Altman analysis demonstrated that there was no disagreement between the results of the OdySight visual acuity module and both the 40-cm Sloan ETDRS and 4-m ETDRS tests, with a very low level of bias (0.53 and - 1.53 letters, respectively). The same analysis of contrast sensitivity showed a broader disagreement between the results of the OdySight module and those of the Pelli-Robson test. A McNemar test indicated that there was no significant difference between results obtained by the OdySight Amsler Grid module and those obtained by the paper version for the detection of metamorphopsia and scotoma (p = 1.0 for both)., Conclusion: The results from the TIL-001 study demonstrate good agreement, overall, between the measurements taken by the near visual acuity module and the Amsler grid module of OdySight as compared to currently used gold standards. The contrast sensitivity module of OdySight will require additional investigation. OdySight could be used for remote monitoring of vision between clinic visits and potentially assist in follow-up planning., Funding: Tilak Healthcare funded the study and the Rapid Service Fees., Trial Registration: ClinicalTrials.gov identifier: NCT03457441.

Purpose: To report the real-world effectiveness and safety of ranibizumab 0.5 mg in patients with visual impairment due to diabetic macular edema (DME)., Methods: This is a French, 36-month, multicenter, observational cohort study. Between December 2013 and April 2015, ophthalmologists enrolled diabetic patients aged ≥18 years with DME-related visual impairment and for whom ranibizumab 0.5 mg was initiated. Here, we present the 12-month results from this cohort. The primary endpoint was the mean change in best-corrected visual acuity (BCVA); sample size calculations were based on RESTORE trial data (BCVA mean change = 6.8 letters, preci sion = 0.7 letters). Secondary endpoints included the change in central subfield thickness (CSFT), number of visits, number of injections received, and frequency of ocular and nonocular adverse events and serious adverse events., Results: Between December 2013 and April 2015, a total of 290 patients with DME were enrolled by 84 ophthalmologists; 12-month data are available for 242 patients (due to low recruitment rates, precision was recalculated for 242 evaluable patients: the precision was then of 1.0 letters). Mean age (± standard deviation) was 66.1 ± 11.0 years and 56.6% were male. The mean baseline BCVA and CSFT were 59.2 letters (95% confidence interval [CI] 57.3, 61.0) and 457 μm (95% CI: 438, 476), respectively. At month 12, the mean gain in BCVA from baseline was 7.4 letters (95% CI: 5.4, 9.4), with 36.8% of patients with BCVA > 70 letters versus 13.2% at baseline. Mean change in CSFT was -125 μm (95% CI: -146, -103). The mean number of ranibizumab injections was 5.1 ± 2.3 over an average of 10.4 ± 3.0 visits. No new safety findings were identified., Conclusions: The BOREAL study confirms the effectiveness and safety of ranibizumab for the treatment of DME-related visual impairment in routine clinical practice with fewer injections than reported in clinical trials., (© 2019 S. Karger AG, Basel.)

Introduction: Current screening recommendations for chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy are based on central 10°C static perimetry and a high-resolution SD-OCT with a special attention to the inferior part of the macula where the toxicity usually starts by ellipsoid zone disruption. However, Melles and Marmor, have recently shown a great variability in the topography of the initial toxicity observed among various ethnicities, which is important to keep in mind so as not to miss early toxicity in certain subgroups of patients., Methods: Review of the literature., Results: Ethnic differences have been shown regarding the topography of the initial retinal toxicity of CQ and HCQ, particularly between Caucasian and Asian subjects. In Caucasians, the first signs of toxicity are more often localized in the inferior para-foveal area associated with a decrease in retinal sensitivity in the upper 10°C visual field. However, in Asian subjects, the first signs of toxicity appear more pericentral (still inferior) with an extramacular pattern that could be missed by the usual 10°C visual field screening., Discussion/conclusion: The pathophysiology of these ethnic differences is unknown and may be due to distinct genetic predisposition to CQ and HCQ toxicity. Screening strategies should be adjusted to the ethnicity and performed in Asian subjects with larger visual fields (30°C), along with SD-OCT, looking for ellipsoid disruption≥8°C from the fovea. The recognition of this pericentral topography and an adjusted screening protocol should avoid late diagnosis in Asians treated with CQ and HCQ., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

The goal of this manuscript is to assess data suggesting that intravitreal injection of anti-vascular endothelial growth factors (anti-VEGFs) could result in systemic adverse events (AEs). The class-specific systemic AEs should be similar to those encountered in cancer trials. The most frequent AE observed in oncology, hypertension and proteinuria, should thus be the most common expected in ophthalmology, but their severity should be lower because of the much lower doses of anti-VEGFs administered intravitreally. Such AEs have not been frequently reported in ophthalmology trials. In addition, pharmacokinetic and pharmacodynamic data describing systemic diffusion of anti-VEGFs should be interpreted with caution because of significant inconsistencies reported. Thus, safety data reported in ophthalmology trials and pharmacokinetic/pharmacodynamic data provide robust evidence that systemic events after intravitreal injection are very unlikely. Additional studies are needed to explore this issue further, as much remains to be understood about local and systemic side effects of anti-VEGFs., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Introduction: Recommendations for screening for chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy have recently been changed by the American Academy of Ophthalmology, taking into account new published data on toxicity prevalence, risk factors, location of onset in the retina and the efficacy of screening tests., Methods: Literature review., Results and Discussion: The risk of developing CQ or HCQ retinopathy depends on the daily dose and duration of treatment. At recommended doses, the risk is<1 % at 5 years, <2 % at 10years but increases to about 20 % after 20years of treatment. The maximum recommended daily dose is 5.0mg/kg for HCQ and 2.3mg/kg for CQ. The two main risk factors are the daily dose and duration of treatment. The presence of kidney failure and treatment with tamoxifen are also significant risk factors. A baseline examination should be performed at the initiation of treatment to rule out pre-existing maculopathy. The screening is then annual and starts from the 5th year of treatment. The two tests recommended for screening are the automated visual field and spectral domain OCT. Multifocal ERG and autofluorescence fundus imaging are only carried out secondarily to confirm the pathology., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Retinal venous occlusions comprise central retinal vein occlusion, hemiretinal vein occlusions, and branch retinal vein occlusions. They are associated with arterial hypertension and glaucoma. Retinal vein occlusions occur more frequently in males, at a median age of 55. The pathogenesis of retinal venous occlusions remains obscure. The clinical presentation of the disease is variable. In most cases, there is a unilateral visual loss over days with a painless, white and quiet eye. However, retinal venous occlusions may also present as an abrupt and profound loss of vision, or be asymptomatic. The course of the disease may be chronic, often with exacerbations. The most severe complication is the onset of extensive capillary non-perfusion, with a high risk of neovascular glaucoma. The most frequent complication is macular edema due to breakdown of the blood-retinal barrier, which can originate from the macula itself and/or from the disc. The treatment is symptomatic. Retinal venous occlusions may resolve either because of the recanalization of the affected vein, or because of the establishment of an efficient collateral circulation. Intravitreal anti-VEGF antibodies or steroids may transiently improve vision, as well as laser photocoagulation, focused or not on macroaneurysms. Visual sequelae are frequent., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Aims: In longstanding diabetic macular oedema (DME) or retinal vein occlusion (RVO), capillary macroaneurysms may develop. Indocyanine green angiography (ICGA) has been shown to optimise their detection. Here, we report the anatomical and functional outcome of the elective photocoagulation of capillary macroaneurysms., Methods: A retrospective, interventional, two-centre study. In eyes with chronic macular oedema and severe hard exsudates due to diabetic retinopathy or RVO, the presence of capillary macroaneurysms (defined by a diameter larger than 150 µm) was assessed by ICGA and optical coherence tomography (OCT). Capillary macroaneurysms were selectively photocoagulated, the presence of photothrombosis within the lumen being assessed by immediate OCT., Results: Four eyes from three patients with DME and five eyes from five patients with RVO were included. The median duration of visual loss was 4 years. Median initial visual acuity (VA) was 20/200. The median number of capillary macroaneurysms per eye was 2 (range, 1-8) and their median size was 410 µm (range, 154-603). Six months after photocoagulation, there was a significant reduction in macular thickness (mean±SD, 528 µm±200 vs 271 µm±152, p<0.05) and improvement of VA (mean log MAR, 0.82 vs 0.58, p<0.05)., Conclusions: During macular oedema with severe hard exsudates due to DME or RVO, systematic detection of capillary macroaneurysms by ICGA followed by their OCT-controlled photocoagulation may be of interest. These results may contribute to re-evaluate the role of photocoagulation in the management of longstanding macular oedema., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Competing Interests: J.-F. Girmens déclare avoir une participation financière au capital de l’entreprise TILAK HealthCare, et intervenir ponctuellement pour Alcon, Allergan, Bayer et Novartis.

Importance: Arteriovenous nickings (AVNs) in the retina are the cause of retinal vein occlusions and are also surrogates of cerebrovascular aging. The prevalent mechanistic model of AVNs stating that arteries crush veins remains somewhat unchallenged despite the lack of evidence other than fundus photographs. Here, we observed that venous nicking may be observed in the absence of physical contact with an arteriole., Observations: This observational study, conducted from January 2013 to September 2014, included 7 patients showing remodeling of a venous segment close to a retinal arteriole without arteriovenous overlap were imaged by adaptive optics imaging. Affected venous segments showed a variable association of nicking, narrowing, deviation, and opacification. Venous segments were deviated toward the arterioles in 6 of the 7 cases. The degree of venous narrowing ranged from 40% to 77%, while at these sites, the width of the intervascular space ranged from 16 µm to 42 µm. Similar features were identified in typical AVNs., Conclusions and Relevance: Arteriovenous nickings do not necessarily involve an arteriovenous compression. Instead, the topology of venous changes suggests a retractile process originating in the intervascular space. These findings have important implications for the understanding of retinal vein occlusions and of cerebrovascular aging.

Background: In recent years, intravitreal injections have added to the treatment modalities available for macular edema (ME) secondary to retinal vein occlusion (RVO). This article aims to provide an update regarding the management of ME secondary to RVO., Methods: A work group met in order to analyze the literature available on Embase/PubMed, regarding treatments for venous occlusion that have received market approval and are reimbursed in France. In total, 33 articles were selected. Consensus within the group for recommendations was based on this data from the literature review and clinical experience and was reported in this article., Results: The management of ME secondary to branch retinal vein occlusion (BRVO) or central vein occlusion of the retina (CRVO) differs on a number of points. Methods of best practice were discussed separately for BRVO and CRVO, taking into account various ocular and associated parameters., Discussion: Ranibizumab and dexamethasone implant are the first-line treatments for visual impairment due to ME secondary to RVO. The choice of either of these drugs may take into account various ocular and extraocular parameters. A change of treatment to one or the other or to laser may also be considered during follow-up., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Purpose: Neovascular age-related macular degeneration (AMD) is the main cause of central vision loss among individuals aged 50 years or older in developed countries. The aim of this study was to review systematically the effect of bevacizumab compared to ranibizumab in patients with AMD at 1 year., Methods: A systematic review was performed on Medline, Embase, and the Cochrane Library and Trial registers to October 2013. Eligibility criteria for selecting studies were randomised controlled trials (RCT) comparing bevacizumab with ranibizumab in patients with neovascular AMD. Odds ratio (OR) and mean difference (MD) estimates were synthesized under fixed- and random-effects models. Heterogeneity was assessed using the Q statistic and I(2)., Results: Five RCTs were included, representing 2,686 randomised patients. The meta-analysis confirmed the non-inferiority of bevacizumab compared to ranibizumab for change in visual acuity at 1 year (MD 0.57 letters, -1.80 to 0.66, p = 0.37, I(2) = 0 %). Better anatomical results were found for ranibizumab. Bevacizumab was associated with a 34 % increase in the number of patients with at least one serious systemic adverse event (OR 1.34, 1.08 to 1.66, p = 0.01, I(2) = 0 %)., Conclusions: The pooled evidence confirmed that, compared with ranibizumab, bevacizumab was associated with equivalent effects on visual acuity at 1 year and with a higher risk of systemic serious adverse events. The current available data do not show which types of adverse events occur more frequently. In practice, bevacizumab should be used under a risk-management plan until further studies have been carried out to assess accurately the increased risk of systemic adverse events.

Purpose: Prospective evaluation of aqueous flare following intravitreal bevacizumab (Avastin, Genentech Inc., San Francisco, CA, USA) injections in eyes with choroidal neovascularization due to age-related macular degeneration., Patients and Methods: Sixteen eyes of eight patients were recruited. Aqueous humor flare was determined by laser flare meter every month after one intravitreal injection of 1.25mg of bevacizumab at baseline followed by a second injection at month3 (day 100±21days). Four patients received an injection at month6 (±10days), and one patient received an injection at month7., Results: Two months after the first intravitreal bevacizumab injection, flare values decreased from 10±5.57 (mean±standard deviation) to 5.2±1.69photon count/ms (P=0.0207) and from 8.3±3.59 to 5.4±0photon counts/ms, 2months after the second injection (P=0.02)., Conclusion: Significantly decreased aqueous humor flare levels were noted after repeated injections of bevacizumab., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Age-related macular degeneration (AMD) is a leading cause of severe visual impairment in individuals over 50 years in developed countries. Latest advances in imaging techniques have led to improved and accurate diagnosis of AMD. We witness a major breakthrough in the treatment of the neovascular form of AMD with the antiangiogenic (anti-VEGF) drugs. However, no therapy is yet available for the atrophic dry form of AMD. Innovative strategies gene therapy, cell therapy, nanotechnology neuroprotection- and multidisciplinary approaches are emerging to prevent the decline in vision in aging populations and its health implications.

Age-related macular degeneration (AMD) is a leading cause of severe visual impairment and disability in older people worldwide. Although considerable advances in the management of the neovascular form of AMD have been made in the last decade, no therapy is yet available for the advanced dry form of AMD (geographic atrophy). This review focuses on current trends in the development of new therapies targeting specific pathophysiological pathways of dry AMD. Increased understanding of the complex mechanisms that underlie dry AMD will help to address this largely unmet clinical need.

Many drugs are presently tested in the different types of age-related macular degeneration (AMD), i.e. geographic atrophy or exudative AMD. In atrophic AMD, drugs attempt to spare the photoreceptors and the retinal pigment epithelium to prevent the oxidative damages or to suppress the inflammation process. In exudative AMD, some drugs try to challenge the available anti-VEGF drugs but others try to improve the visual prognosis in targeting other mechanisms or cells involved in angiogenesis, such as pericytes. The present article aims to summarize the available data, given in scientific meetings or given by the companies., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Purpose: To correlate retinal function with vascular response to flicker light in normotensive patients with diabetes without diabetic retinopathy (DR)., Methods: Twenty-eight normotensive patients with diabetes (11 with type 1, 17 with type 2) without DR and 28 sex- and age-matched healthy control subjects underwent color vision and contrast sensitivity testing, pattern, full-field, and multifocal electroretinography, and evaluation of the vascular response to flicker light with the dynamic vessel analyzer., Results: In the patients with diabetes, electroretinogram (ERG) pattern responses, b-wave in the scotopic bright flash ERG, a-wave and b-wave in the photopic single-flash ERG, and oscillatory potential responses were significantly impaired compared with those in control subjects. Vascular response to flicker light was also impaired in patients with diabetes compared with controls. In the whole population, correlations were found between flicker light-induced arterial retinal vasodilation and the amplitude and implicit time of the N95 wave of pattern ERG (r = -0.27, P = 0.047 and r = -0.35, P = 0.008, respectively), the b-wave implicit time of rod ERG (r = -0.36; P = 0.01) and the oscillatory potentials (r = 0.4; P = 0.003), suggesting that impairment of the vascular response to flicker light may reflect inner retinal neural impairment. However, no correlation between these factors was found when only patients with diabetes were considered., Conclusions: In patients with diabetes, neural and neurovascular dysfunctions both precede the onset of clinically detectable DR. To which extent these abnormalities are related to each other remains to be determined. (ClinicalTrials.gov number, NCT00839150.)

Background: Macular edema occurring after retinal vein occlusion (RVO) or diabetic retinopathy (DR) may be due to the development of capillary and/or venous macroaneurysms (MAs). Here, we investigated the respective contribution of fluorescein angiography (FA), of indocyanine green angiography (ICGA) and of high-resolution optical coherence tomography (HR-OCT) to their detection., Methods: Review of the charts of six consecutive patients with MAs secondary to RVO (n = 4) or DR (n = 2). For each patient, FA, ICGA and HR-OCT data were analyzed and compared., Results: All detectable MAs were detected by ICGA, while in three eyes FA failed to show them. Overall, ICGA provided a better delineation of MAs than FA. In all cases, HR-OCT identified MAs under the form of a vascular structure with a reflective wall surrounding a lumen containing variably reflective material., Conclusions: MAs can develop during the course of RVO and DR. ICGA and HR-OCT improves the identification of capillary and venous MAs, and may thus be of interest to better identify sites of blood-retinal barrier rupture during chronic macular edema due to RVO or DR.

In eye core lens membranes, aquaporin-0 (AQP0) and connexins (Cx) form together well-structured supramolecular assemblies, the junctional microdomains, in which they assure water, ion, metabolite, and waste transport. Additionally, they mediate cell-cell adhesion-forming thin junctions (AQP0) and gap junctions (Cx). We have used atomic force microscopy and biochemical methods to analyze and compare the structure of junctional microdomains in human cataract lens membranes from a type II diabetes patient and healthy lens membranes from calf. A healthy intercellular junctional microdomain consists in average of approximately 150 tetragonally arranged (a = b = 65.5 A, gamma = 90 degrees) AQP0 tetramers surrounded by densely packed non-ordered connexon channels. Gap-junction connexons act as lineactants inside the membrane and confine AQP0 in the junctional microdomains. In the diabetic cataract lens, connexons were degraded, and AQP0 arrays are malformed. We conceptualize that absence of connexons lead to breakdown of cell nutrition.

Recent observations have found that premacular hemorrhage in Valsalva retinopathy is located under the internal limiting membrane. We confirm these findings in two case reports of Valsalva retinopathy. Visual acuity rehabilitation was obtained in the first case by conservative treatment and by draining the hemorrhage into the vitreous with Neodymium (Nd):Yag laser in the second case. We report the current therapeutic guidelines for Valsalva retinopathy, including the systematic search of autosomal dominant syndrome of retinal arterial tortuosity, a rare condition, often discovered after this type of benign macular hemorrhage.

Aim: To report four cases of central retinal vein occlusion (CRVO) in a French family., Patients and Methods: Ophthalmological examination and medical work-up of seven members of the family., Results: There were four cases of CRVO in two consecutive generations. Three of them had CRVO in both eyes. Arterial hypertension was present in two, associated to glaucoma in one. Medical work-up did not reveal additional risk factors., Conclusions: We report a case of familial clustering of CRVO. Our cases combined to other cases reported in the literature provide arguments for the existence in some subjects of a genetic predisposition of CRVO. Additional case series are however needed to confirm this hypothesis.

Purpose: The pathophysiology and causes of retinal vein occlusion (RVO) remain largely unknown. Latent forms of myeloproliferative disorders, which are diagnosed by the presence of in vitro endogenous erythroid colony (EEC) formation, are a well-known cause of intraabdominal vein thrombosis. The suspected diagnosis of a latent myeloproliferative disorder in a patient with RVO, based on the presence of EEC formation, led us to evaluate the association between latent myeloproliferative disorders and RVO., Design: Observational case series in a national eye center., Participants: Forty-four patients, with a mean age of 46 years (range, 21-62) and central (n = 38) or peripheral (n = 6) RVO responsible for visual acuity decreased to 6/12 or less., Methods: In vitro bone marrow culture., Main Outcome Measure: Endogenous erythroid colony formation in cytokine-free culture medium. Conventional diagnostic criteria for myeloproliferative disorders and the JAK2 V617F mutation (which is strongly associated with myeloproliferative disorders) were assessed in RVO patients showing EECs., Results: Endogenous erythroid colony formation was observed in 12 of 44 (27%) patients with RVO, 13 of 35 (37%) patients with Budd-Chiari syndrome, and 52 of 53 (98%) patients with primary polycythemia (positive control groups) but not in 22 healthy bone marrow donors (negative controls) evaluated at the same time and by the same hematology laboratory. Neither conventional nor genetic diagnostic criteria for myeloproliferative disorders were observed in any patient with both RVO and an EEC at the time of diagnosis or during follow-up., Conclusions: Endogenous erythroid colony formation is frequently observed in patients with RVO independently of any detectable myeloproliferative disorder. This opens a new aspect of research on the pathophysiology of this sight-threatening disease.

Human pathologies often originate from molecular disorders. Therefore, imaging technology as one of the bases for the identification and understanding of pathologies must provide views of single molecules at subnanometer resolution. Membrane proteins mediate many of life's most important processes, and their malfunction is often lethal or leads to severe disease. The membrane proteins aquaporin-0 (AQP0) and connexons form junctional microdomains between healthy lens core cells in which AQP0 form square arrays surrounded by connexons. Malfunction of both proteins results in the formation of cataract. We have used high-resolution atomic force microscopy (AFM) to image junctional microdomains in membranes from an individual human eye lens with senile cataract. Images at subnanometer resolution report individual helix-connecting loops of four amino acid residues on the AQP0 surface. We describe the supramolecular assembly and the conformational state of AQP0 in junctional microdomains, where a mixture of truncated junctional and full-length water channel AQP0 form square arrays. Imaging of microdomain borders revealed individual AQP0 tetramers and no associated connexon, indicating a lack of metabolite transport, waste accumulation, and enlarged regions of non-adhering membranes, causing cataract in this individual. This first high-resolution view of the membrane of this pathological human tissue provides insights into cataract pathology at the single membrane protein level, and indicates the power of the AFM as a future tool in medical imaging at subnanometer resolution.

Introduction: To evaluate the tolerance and efficacy of heavy silicone oil as internal tamponade for retinal detachment surgery., Patients and Methods: Sixty-six eyes requiring heavy silicone oil for retinal detachment, with at least 1 month follow-up, were retrospectively studied. Preoperative status, surgical technique, tolerance, and anatomical and functional results were analyzed from the patient's file. Indications for heavy silicone injection were inferior retinotomy or inferior retraction in 65% of cases. PVR grade C was present in at least 63% of cases. Retinotomy was performed in 45% of cases. An exchange procedure was performed versus DKline in 65% of cases. Mean follow-up was 7 +/- 4 months., Results: At the end of follow-up, 59% of eyes had a completely reattached retina, 32% without internal tamponade. Another surgery was necessary in 54% of cases. During follow-up, mean intraocular pressure was normal, and there was a significant intraocular inflammation in three cases (4.5%). In seven cases of the 44 ablations of heavy silicone oil, an adherence of residual bubbles was present. Redetachment occurred after ablation for anatomical success in 41% of cases. BCVA was better than 0.05 (20/400) in 54% of cases at the end of follow-up., Conclusion: Heavy silicone was well tolerated and seems not to be pro-inflammatory in our study. It is a good alternative to standard silicone for inferior retinotomy and inferior breaks without PVR. It is not a treatment of inferior retraction, and is not a long-term internal tamponade. During the ablation of heavy silicone oil, adherence of residual bubbles is possible, in which case a coaxial light or an endoillumination could be needed during ablation.

Purpose: To report in four patients with retinal vein occlusion the presence of biomicroscopically visible circulation in the minor arterial circle of the iris, preceding rubeosis iridis in two cases., Design: Retrospective observational case series., Methods: Four patients with ischemic type of central or hemi-central retinal vein occlusion seen at a single center., Results: Dilation of the minor arterial circle remnants with biomicroscopically visible circulation was observed in four eyes of four adult patients with severe retinal ischemia secondary to retinal vein occlusion and preceded the occurrence of anterior segment neovascularization in two cases., Conclusion: In patients with ischemic retinal vein occlusion, the clinical finding of a dilation of the minor arterial circle may indicate the necessity of a closer follow-up to make a timely decision on panretinal photocoagulation.

Purpose: To test the efficacy of the novel vascular endothelial growth factor (VEGF) receptor inhibitor SU5416, in a case of refractory von Hippel-Lindau (VHL) retinal hemangioblastoma (RHB)., Design: Interventional case report., Methods: Patient included in a multicenter phase II trial. A 30-year-old woman presenting with VHL disease and multiple RHB on her only eye, refractory to conventional treatments, had decreased visual acuity due to cystoid macular edema (CME). SU5416 was administered intravenously for 7 months. Best-corrected visual acuity (BCVA) and macular thickness were measured by optical coherence tomography., Results: Under treatment, the size of the RHB did not change, but CME improved significantly. Best-corrected visual acuity rose from 20/40 to 20/25. However, CME recurred after the end of the treatment., Conclusion: The VEGF receptor inhibitor SU5416 failed to reduce the size of RHB but was very effective for the associated CME.

Purpose: To investigate the possible persistence and characteristics of infrared fluorescence of the fundus for several months after surgery with intraocular injection of indocyanine green (ICG)., Design: Interventional, noncomparative, prospective case series., Participants: Seventeen patients operated on in our department with ICG injection into the vitreous cavity, who gave prior informed consent., Methods: After standard three-port pars plana vitrectomy and posterior vitreous detachment, 0.1 to 0.2 ml of an ICG solution at a concentration of 2.5 mg/ml was injected through a 5- micro m sterile filter over the posterior pole and left in place for 3 minutes. The stained internal limiting membrane was then peeled off. Patients had postoperative infrared fundus photographs at each consultation in our department. Follow-up ranged from 1 to 7 months. Visual acuity and any unexpected event were also recorded., Main Outcome Measures: Postoperative infrared fluorescence of the fundus., Results: The day after surgery, no green ICG staining of the fundus was visible on biomicroscopy. However, infrared photography showed diffuse fluorescence of the fundus. At 1 and 3 postoperative months, infrared fundus photography showed an intensely fluorescent optic nerve disc. In patients with macular hole, the center of the macula also exhibited faint granular fluorescence. At 6 months postoperative or later, only the optic disc remained fluorescent, but the fluorescence was far less intense than at 3 months. Infrared photographs of the fellow eyes exhibited no fluorescence. Visual acuity improved or was unchanged compared with preoperative vision in 16 eyes and decreased by 1 line in 1 eye., Conclusions: After intraoperative use of ICG for macular surgery, fluorescence of the optic disc and of the macular center after macular hole surgery persisted for months in all cases. ICG may accumulate in the macular pigment epithelium and optic nerve, raising the problem of the as yet unknown pharmacokinetics of ICG after intravitreous administration and of its long-term safety.