Publications by authors named "Ramin Tadayoni"

147 Publications

Surgical outcomes in patients with lamellar macular holes selected based on the optical coherence tomography consensus definition.

Int J Retina Vitreous 2021 Apr 13;7(1):31. Epub 2021 Apr 13.

Ophthalmology Department, AP-HP, Hôpital Lariboisière, Université de Paris, 2 rue Ambroise Paré, 75010, Paris, France.

Purpose: The surgical indication for lamellar macular holes (LMH) is controversial due to a misclassification of different macular diseases. A consensus based on an optical coherence tomography (OCT) definition has recently been suggested. The aim of this study was to investigate the surgical outcomes of patients with LMH selected based on this OCT-based consensus definition.

Methods: Retrospective review of patients who underwent surgery for LMH with a follow-up of at least 3 months. Anatomical OCT criteria for the diagnosis of LMH were the presence of an irregular foveal contour with foveal cavitation and a loss of retinal tissue. Cases of macular pseudoholes and epiretinal membrane foveoschisis were excluded. Surgery consisted in pars plana vitrectomy with centripetal peri-hole peeling of epiretinal proliferation and internal limiting membrane. Pre- and postoperative visual acuities (VA) were compared, and changes in OCT anatomical features, including the restoration of the foveal profile and outer retinal layers, were assessed.

Results: Eleven eyes of 11 patients were included, of which 9 eyes (81.8%) showed proliferation on preoperative OCT. The mean VA improved from 0.44 ± 0.19 LogMAR (20/55 Snellen equivalent) to 0.16 ± 0.08 LogMAR (20/28 Snellen equivalent), after a mean follow-up of 7.2 ± 2.9 months (P = 0.02). Postoperatively, all eyes showed a restored foveal profile. The mean central foveal thickness increased from 127.6 ± 29.9 μm to 209.0 ± 44.0 μm (P = 0.001). At baseline, ellipsoid zone disruption and external limiting membrane disruption were found in 9 and 7 eyes, respectively. Postoperatively, the ellipsoid zone and external limiting membrane were restored in respectively 6/9 eyes (66.7%) and 5/7 eyes (71.4%). No cases of postoperative full-thickness macular hole were found.

Conclusion: In patients with LMH carefully selected based on the recent OCT-based criteria and showing a loss of retinal tissue, the foveal architecture was restored and the VA was improved after vitrectomy with peri-hole peeling for epiretinal proliferation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40942-021-00297-6DOI Listing
April 2021

Preoperative imaging optimized for epiretinal membrane surgery.

Int J Retina Vitreous 2021 Apr 13;7(1):32. Epub 2021 Apr 13.

Ophthalmology Department, AP-HP, Hôpital Lariboisière, Université de Paris, 75010, Paris, France.

Background: To compare imaging modalities for visualizing primary epiretinal membrane (ERM) with each other and with intraoperative digital images (IDI) after blue staining.

Methods: The records of consecutive patients operated for primary ERM over a 12-month period were retrospectively reviewed. Preoperative imaging included color fundus photography (CFP), En Face spectral-domain optical coherence tomography (OCT), 45° infrared- (IR) and blue-reflectance (BR) scanning laser ophthalmoscopy. All images were qualitatively analyzed and scored from 0-4 according to the ability to visualize ERM details (0 = no visible ERM or vessel contraction, 1 = vessel contraction, 2 = retinal folds, 3 = ERM limits, 4 = elevated ERM edge). The preoperative ERM morphology was then compared to that seen on the IDI acquired after 1-min blue dye staining when available.

Results: Seventy eyes were included. The highest score for ERM visualization was obtained on BR and En Face OCT. A score of 3 or 4 was obtained in 68.5%, 62.1%, 17.9% and 13.6% of cases on En Face OCT, BR, CFP and IR images, respectively. IDI were available for 20 eyes, and showed a similar ERM morphology compared to preoperative images in most cases: a negative staining pattern corresponded to a plaque on En face OCT in 91% of eyes. However, IDI failed to show the ERM edges in 37.5% of cases.

Conclusion: ERM morphology was better visualized preoperatively by BR and En Face OCT, in a similar way to the IDI after staining. Future intraoperative visualization systems could integrate both imaging modalities overlaid with the IDI for guiding ERM removal instead of staining.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40942-021-00304-wDOI Listing
April 2021

Reproducing diabetic retinopathy features using newly developed human induced-pluripotent stem cell-derived retinal Müller glial cells.

Glia 2021 Mar 8. Epub 2021 Mar 8.

Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France.

Muller glial cells (MGCs) are responsible for the homeostatic and metabolic support of the retina. Despite the importance of MGCs in retinal disorders, reliable and accessible human cell sources to be used to model MGC-associated diseases are lacking. Although primary human MGCs (pMGCs) can be purified from post-mortem retinal tissues, the donor scarcity limits their use. To overcome this problem, we developed a protocol to generate and bank human induced pluripotent stem cell-derived MGCs (hiMGCs). Using a transcriptome analysis, we showed that the three genetically independent hiMGCs generated were homogeneous and showed phenotypic characteristics and transcriptomic profile of pMGCs. These cells expressed key MGC markers, including Vimentin, CLU, DKK3, SOX9, SOX2, S100A16, ITGB1, and CD44 and could be cultured up to passage 8. Under our culture conditions, hiMGCs and pMGCs expressed low transcript levels of RLPB1, AQP4, KCNJ1, KCJN10, and SLC1A3. Using a disease modeling approach, we showed that hiMGCs could be used to model the features of diabetic retinopathy (DR)-associated dyslipidemia. Indeed, palmitate, a major free fatty acid with elevated plasma levels in diabetic patients, induced the expression of inflammatory cytokines found in the ocular fluid of DR patients such as CXCL8 (IL-8) and ANGPTL4. Moreover, the analysis of palmitate-treated hiMGC secretome showed an upregulation of proangiogenic factors strongly related to DR, including ANG2, Endoglin, IL-1β, CXCL8, MMP-9, PDGF-AA, and VEGF. Thus, hiMGCs could be an alternative to pMGCs and an extremely valuable tool to help to understand and model glial cell involvement in retinal disorders, including DR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/glia.23983DOI Listing
March 2021

Postoperative outcomes of idiopathic epiretinal membrane associated with foveoschisis.

Br J Ophthalmol 2021 Feb 17. Epub 2021 Feb 17.

Université de Paris, Ophthalmology Department, AP-HP, Hôpital Lariboisière, F-75010, Paris, France

Aims: To analyse the prevalence and postoperative outcomes of a particular form of epiretinal membrane (ERM) with foveoschisis-like stretched hyporeflective spaces in emmetropic eyes.

Methods: A retrospective study of all consecutive eyes operated for primary ERM over a 46-month period was conducted. The presence of foveoschisis-like stretched hyporeflective spaces was assessed on the preoperative optical coherence tomography B-scan in all eyes. Highly myopic eyes were excluded. Preoperative and postoperative characteristics of eyes with foveoschisis were compared with those of a control group of 100 consecutive eyes with primary ERM without cystoid spaces.

Results: Of 544 eyes with primary ERM, 17 had foveoschisis, corresponding to a prevalence of 3.1%. After a mean postoperative follow-up of 17.9±10.9 months, the foveoschisis had completely resolved in 76.5% of eyes (n=13/17). In the four eyes (23.5%) with persistent foveoschisis, the remaining hyporeflective cystoid spaces were located exclusively in the inner nuclear layer. The postoperative visual acuity and central macular thickness did not differ between both groups at the final visit. However, an acute postoperative macular oedema occurred in 24% (n=4/17) of cases (vs 3% in the control group; p=0.0084).

Conclusion: Foveoschisis was found in about 3% of eyes with idiopathic ERM. After peeling, the foveoschisis usually resolves completely with functional outcomes similar to those achieved with other primary ERM. However, this feature was associated with a higher risk of postoperative macular oedema (in 1/4 of cases).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bjophthalmol-2020-317982DOI Listing
February 2021

Functional and anatomical outcomes after successful repair of macula-off retinal detachment: a 12-month follow-up of the DOREFA study.

Acta Ophthalmol 2021 Feb 11. Epub 2021 Feb 11.

Department of Ophthalmology, University Hospital, Dijon, France.

Purpose: To report visual and anatomical outcomes and determine predictors of good visual acuity (VA) recovery after macula-off rhegmatogenous retinal detachment (RD).

Methods: Prospective multicentre study including 115 eyes from 115 patients successfully operated on for RD, with assessment of VA and spectral-domain optical coherence tomography (SD-OCT) macular images at 1, 3, 6 and 12 months after surgery.

Results: Over the follow-up period, VA significantly improved from median [IQR] 62 [46; 72] ETDRS letters at 1 month to 75 [67; 80] ETDRS letters at 12 months (p < 0.001) with a concomitant decreased number of eyes with any SD-OCT lesions (p < 0.001). The presence of subretinal fluid (SRF) significantly decreased (p < 0.001), as did the number of photoreceptor (PR) layer lesions (p = 0.04). At 12 months, lesions in the PR layer and poor VA recovery were significantly associated with a longer time to surgery (p = 0.007 and p < 0.001, respectively). The rate of patients without PR lesions increased from 40.9% at 1 month to 60.0% at 6 months and 73.9% at 12 months (p < 0.001). The incidence of epiretinal membrane (ERM) significantly increased (p < 0.001), while cystoid macular oedema (CME) remained stable over time. Visual acuity (VA) at 3 months postoperatively was a good reflection of final VA recovery (p < 0.001).

Conclusion: Visual acuity (VA) improved in parallel with the decreasing number of eyes with SD-OCT lesions after macula-off rhegmatogenous RD. A long time to surgery was the only preoperative factor associated with poor VA recovery after retinal detachment surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aos.14777DOI Listing
February 2021

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

Pharmaceutics 2021 Feb 1;13(2). Epub 2021 Feb 1.

Department of Ophthalmology, Croix-Rousse University Hospital, 69004 Lyon, France.

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% ( = 96) of patients whose average VA gain was less than five letters and Group B, with 29% ( = 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 ( = 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, = 0.002) but without a significant difference in VA gain (4.9 letters versus 6.8, = 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pharmaceutics13020194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912784PMC
February 2021

Long-term capillary changes in areas of dissociated optic nerve fibre layer after macular hole surgery.

Acta Ophthalmol 2021 Jan 10. Epub 2021 Jan 10.

Department of Medical, Surgical, and Experimental Sciences, Ophthalmology Unit, University of Sassari, Sassari, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aos.14750DOI Listing
January 2021

Spontaneous Conversion of Lamellar Macular Holes to Full-Thickness Macular Holes: Clinical Features and Surgical Outcomes.

Ophthalmol Retina 2021 Jan 5. Epub 2021 Jan 5.

Department of Ophthalmology, Palo Alto Medical Foundation, Palo Alto, California. Electronic address:

Purpose: To describe the clinical features and surgical outcomes of patients experiencing a spontaneous conversion of a lamellar macular hole (LMH) to a full-thickness macular hole (FTMH).

Design: Retrospective, multicenter, observational case series.

Participants: Patients with LMH who experienced a spontaneous conversion to FTMH and underwent FTMH surgery.

Methods: Clinical charts and OCT features of 20 eyes of 20 patients were reviewed.

Main Outcome Measures: OCT features and surgical outcomes of FTMH derived from LMH.

Results: The mean baseline visual acuity (VA) was 0.21 ± 0.19 logarithm of the minimum angle of resolution (logMAR) (20/32 Snellen equivalent [SE]). Epiretinal proliferation was noted in 18 eyes (90%), and 14 eyes (75%) had an epiretinal membrane. At the diagnosis of FTMH, the mean VA decreased to 0.61 ± 0.50 logMAR (20/81 SE) (P = 0.001). The mean FTMH diameter was 224.4 ± 194.8 μm, with 15 (75%) small (≤250 μm), 2 (10%) medium (>250-≤400 μm), and 3 (15%) large (>400 μm) FTMHs. Eighteen (90%) FTMHs were sealed after 1 surgery, and 2 (10%) required an additional procedure. At the last follow-up, the mean VA was increased to 0.29 ± 0.23 logMAR (20/38 SE) (P = 0.003), but did not significantly differ from the baseline VA (P = 0.071).

Conclusions: Patients with LMH may develop an FTMH with no evidence of vitreomacular traction. A tangential traction from an epiretinal membrane may contribute to its genesis, but a progressive loss of retinal tissue and an inherent weakness of the foveal architecture in LMH eyes could be sufficient. Most FTMHs derived from LMH had a small diameter, showed epiretinal proliferation, showed limited retinal hydration, and were associated with relatively poor surgical outcomes compared with idiopathic FTMH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.oret.2020.12.023DOI Listing
January 2021

Standardization of OCT Angiography Nomenclature in Retinal Vascular Diseases: First Survey Results.

Ophthalmol Retina 2021 Jan 1. Epub 2021 Jan 1.

Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Bern Photographic Reading Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Purpose: To develop a consensus nomenclature for OCT angiography (OCTA) findings in retinal vascular diseases.

Design: Online survey using the Delphi Method.

Participants: Members of The Retina Society, the European Society of Retina Specialists, and the Japanese Retina and Vitreous Society.

Methods: An online questionnaire on OCTA terminology in retinal vascular diseases was sent to members of The Retina Society, the European Society of Retina Specialists, and the Japanese Retina and Vitreous Society. The respondents were divided into 2 groups ("experts" vs. "users") according to the number of their publications in this field. The respondents who had more than 5 publications in the field of OCTA and retinal vascular diseases were considered the OCTA "experts" group.

Main Outcome Measures: Consensus and near consensus on OCTA nomenclature.

Results: The complete responses of 85 retina specialists were included in the analysis. Thirty-one were categorized as "experts." There was a consensus in both groups that OCTA parameters such as foveal avascular zone (FAZ) parameters, areas of nonperfusion, and presence of neovascularization (NV) should be implemented in the identification and staging of diabetic retinopathy (DR) and that OCTA can be applied to differentiate between ischemic and nonischemic retinal vein occlusion (RVO). Diabetic macular ischemia (DMI) also can be assessed via OCTA. Further, there was consensus that the terminology should differ on the basis of the underlying causes of decreased vascular flow signal. There was disagreement in other areas, such as which terms should be applied to describe decreased OCTA signal from different causes, the definition of wide-field OCTA, and how to quantify DMI and area of decreased flow signal. These discrepancies form the basis for the upcoming expert Delphi rounds that aim to develop a standardized OCTA nomenclature.

Conclusions: Although there was agreement in some areas, significant differences were found in many areas of OCTA terminology among all respondents, but also between the expert and user groups. This indicates the need for standardization of the nomenclature among all specialists in the field of retinal vascular diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.oret.2020.12.022DOI Listing
January 2021

Need for a New Classification of Diabetic Retinopathy.

Retina 2021 Mar;41(3):459-460

Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, California.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/IAE.0000000000003070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889282PMC
March 2021

Evolution of Dome-shaped Macula Is Due to Differential Elongation of the Eye Predominant in the Peri-dome Region.

Am J Ophthalmol 2020 Dec 4;224:18-29. Epub 2020 Dec 4.

Department of Ophthalmology, New Civil Hospital, Strasbourg University Hospital, FMTS, Strasbourg, France. Electronic address:

Purpose: To determine the mechanism behind macular bulge height increase in eyes with dome-shaped macula (DSM).

Design: Retrospective, observational case series.

Methods: Eyes presenting with DSM followed up for a minimum of 1 year were examined using ocular biometry and spectral-domain optical coherence tomography at baseline and at end of follow-up. Axial length (AL), DSM bulge height, and central and peripheral choroidal thickness (nasal, temporal, superior, and inferior quadrants) were reported. Eyes were categorized into 2 groups for comparison: the "mini-DSM" group (DSM < 100 μm) and the "classic" DSM group (DSM > 100 μm).

Results: Fifty-eight eyes (33 patients) were studied: 32 (55%) were classic DSM and 26 (45%) mini-DSM. During the mean follow-up of 51.76 ± 36.01 months, mean AL increased from 26.99 ± 2.94 mm to 27.12 ± 3.09 mm (P = .010) and mean macular bulge height increased from 235.88 ± 282.47 μm to 262.34 ± 317.15 μm (P < .001). DSM height change was significantly higher than AL change (P < .001). Mean peripheral choroidal thickness significantly decreased nasally (P = .008), temporally (P = .026), and inferiorly (P < .001). Mini-DSM eyes exhibited shorter AL (26.17 vs 27.66 mm; P = .027), greater visual acuity (0.169 vs 0.437 logMAR; P = .002), and fewer macular complications compared to classic DSM eyes.

Conclusions: Macular bulge increase in DSM is associated with eye elongation and overall thinning of the peripheral choroid. DSM might result from differential elongation of the eye predominant in the peri-dome region. Mini-DSM (ie, inferior to 100 μm) are characterized by slower evolution, better visual prognosis, and fewer complications compared to "classic" DSM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajo.2020.11.013DOI Listing
December 2020

Hyperreflective cystoid spaces in diabetic macular oedema: prevalence and clinical implications.

Br J Ophthalmol 2020 Dec 1. Epub 2020 Dec 1.

Universite de paris, Ophthalmology Department, AP-HP, Hôpital Lariboisière, F-75010, Paris, France.

Aims: To analyse the prevalence and evolution of hyper-reflective cystoid spaces with decorrelation signal detected using optical coherence tomography angiography (OCTA) in diabetic macular oedema (DMO).

Methods: A retrospective study of consecutive eyes with DMO imaged using OCTA over a 1-year period was conducted. All eyes with hyper-reflective cystoid spaces at baseline and at least 3 months of follow-up were included in a longitudinal analysis.

Results: The prevalence of hyperreflective cystoid spaces with decorrelation signal was of 37% (61/165) in DMO eyes. Hyperreflective foci within hyperreflective cystoid spaces were observed in 85% of eyes. The longitudinal study included 33 eyes (10 observed and 23 treated with intravitreal anti-vascular endothelial growth factor), with a median follow-up of 15 months. The hyperreflective cystoid spaces resolved in 85% of eyes. The mean best-corrected visual acuity remained stable during the follow-up, even in the eyes achieving a resolution of the hyperreflective cystoid spaces. Hard exudates appeared in the area of resolved hyperreflective cystoid spaces in 33% of eyes.

Conclusion: Hyperreflective cystoid spaces detected by OCTA affected more than one-third of the DMO eyes. Their disappearance was not associated with any functional improvement and led to the formation of new hard exudate deposits in about one-third of the eyes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bjophthalmol-2020-317191DOI Listing
December 2020

Risk of Inflammation, Retinal Vasculitis, and Retinal Occlusion-Related Events with Brolucizumab: Post Hoc Review of HAWK and HARRIER.

Ophthalmology 2020 Nov 15. Epub 2020 Nov 15.

Ophthalmic Consultants of Boston, Boston, Massachusetts. Electronic address:

Purpose: An independent Safety Review Committee (SRC), supported by Novartis Pharma AG, analyzed investigator-reported cases of intraocular inflammation (IOI), endophthalmitis, and retinal arterial occlusion in the phase 3 HAWK and HARRIER trials of brolucizumab versus aflibercept in neovascular age-related macular degeneration (nAMD).

Design: A post hoc analysis of a subset of data from two 2-year, double-masked, multicenter, active-controlled randomized phase 3 trials (NCT02307682, NCT02434328).

Participants: Patients (N = 1817) with untreated, active choroidal neovascularization due to age-related macular degeneration in the study eye were randomized and treated in HAWK/HARRIER. The SRC reviewed data from cases of investigator-reported IOI (60/1088 brolucizumab-treated eyes; 8/729 aflibercept-treated eyes).

Methods: The SRC received details and images (color fundus photography, fluorescein angiography, and OCT) for all investigator-determined cases of IOI, retinal arterial occlusion, and endophthalmitis. Cases were reviewed in detail by ≥2 readers, then adjudicated by the SRC as a group.

Main Outcome Measures: Within this patient subset: incidence of IOI, signs and incidence of retinal vasculitis and/or retinal vascular occlusion, and visual acuity loss; time since first brolucizumab injection to IOI event onset; and frequency of visual acuity loss after brolucizumab injection by time of first IOI event onset.

Results: Fifty brolucizumab-treated eyes were considered to have definite/probable drug-related events within the spectrum of IOI, retinal vasculitis, and/or vascular occlusion. On the basis of these cases, incidence of definite/probable IOI was 4.6% (IOI + vasculitis, 3.3%; IOI + vasculitis + occlusion, 2.1%). There were 8 cases (incidence 0.74%) of at least moderate visual acuity loss (≥15 ETDRS letters) in eyes with IOI (7 in eyes with IOI + vasculitis + occlusion). Of the 8 cases, 5 experienced their first IOI-related event within 3 months of the first brolucizumab injection (increasing to 7/8 within 6 months). Incidence of IOI in aflibercept-treated eyes was 1.1%, with at least moderate visual acuity loss in 0.14%.

Conclusions: This analysis of IOI cases after brolucizumab injection identified signs of retinal vasculitis with or without retinal vascular occlusion and an associated risk of visual acuity loss. The findings will help physicians to evaluate the risks and benefits of brolucizumab treatment for nAMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ophtha.2020.11.011DOI Listing
November 2020

Brolucizumab: A Newly Developed Anti-VEGF Molecule for the Treatment of Neovascular Age-Related Macular Degeneration.

Ophthalmologica 2020 Nov 16. Epub 2020 Nov 16.

Background Despite the success of anti-vascular endothelial growth factors (anti-VEGF), there is currently a need for highly effective compounds that can alleviate the burden of managing neovascular age-related macular degeneration (nAMD). Purpose To review the milestones in the molecular and clinical development of brolucizumab, the first single-chain antibody fragment designed specifically for intraocular use in humans. Methods In this article, we summarize the pre-clinical and current clinical evidence for brolucizumab, with an outlook to other treatment regimens and additional indications under investigation. Results The unique molecular design of brolucizumab led to a low molecular weight of only 26 kDa, allowing for a concentrated molar dosing in one intra-vitreal injection compared with other anti-VEGF agents. The Phase I and II clinical trial outcomes validated the efficacy of brolucizumab in the treatment of nAMD with signals of a more durable treatment effect. The pivotal Phase III trials HAWK and HARRIER, which included a total of 1,817 patients, established that brolucizumab can be administered every 3 months while maintaining disease control. Conclusions The pre-clinical and clinical data for brolucizumab provide evidence of sustained disease control with longer injection intervals, thus potentially reducing the treatment burden in patients with nAMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000513048DOI Listing
November 2020

OCT of Outer Retinal Hyperreflectivity, Neovascularization, and Pigment in Macular Telangiectasia Type 2.

Ophthalmol Retina 2020 Sep 19. Epub 2020 Sep 19.

Department of Ophthalmology, APHP, Hôpital Lariboisière, and Université de Paris, Faculté de Médecine Paris-Diderot, Paris, France; Centre de Référence des maladies Vasculaires rares du Cerveau et de l'Œil (CERVCO), Hôpital Lariboisière, APHP, Paris, France. Electronic address:

Purpose: To investigate whether outer retina hyperreflectivity (ORHR) and outer retina neovascularization (ORNV) are visible in eyes with macular telangiectasia type 2 (MacTel 2) before pigment proliferation is visible.

Design: Retrospective study in a cohort of patients from the MacTel Project.

Participants: Thirty-nine MacTel 2 eyes without pigment on color fundus photography (CFP) at presentation were studied over a mean of 36.6 months (range, 13.8-50.4 months; standard deviation, ±10 months).

Methods: All patients routinely underwent Snellen best-corrected visual acuity (VA) measurement, CFP, spectral-domain OCT, and OCT angiography (OCTA).

Main Outcome Measures: Pigment in the macula on CFP, best-corrected VA, presence of ORHR, presence of ORNV, presence and surface of ellipsoid zone (EZ) loss, and occurrence of ORHR, ORNV, and pigment.

Results: At presentation, 13 eyes showed no EZ loss, and no ORHR nor change was observed during the follow-up. In the 19 eyes with only EZ loss at baseline, ORHR appeared in 6 eyes, and one of them also showed visible pigment on CFP. Among the 7 eyes with ORHR and ORNV at baseline, pigment proliferation became visible in 4 eyes. Overall, at the end of follow-up, 14 eyes showed ORNV and 13 showed ORHR, of which 5 showed pigment on CFP. In all cases, ORHR on spectral-domain OCT corresponded to ORNV on OCTA. Hyperreflectivity and neovascularization developed within an EZ loss area or at its edge. At the end of follow-up, although the EZ loss area was larger in eyes with ORHR, pigment, or both than in eyes without any pigment migration (0.33 mm vs. 0.94 mm; P = 0.01), VA was similar in both groups (0.32 logarithm of the minimum angle of resolution [logMAR] vs. 0.35 logMAR; Snellen equivalent, 20/40 vs. 20/50; P = 0.64).

Conclusions: Spectral-domain OCT and OCTA showed that in MacTel 2 eyes, ORHR was associated with ORNV on OCTA and most often did not correspond to pigmentation on CFP. When ORNV developed, hyperreflectivity appeared along the abnormal capillary tracts after a mean follow-up of 36 months. In most cases, the presence of ORHR was not associated with rapid vision loss.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.oret.2020.09.012DOI Listing
September 2020

Bradykinin 1 Receptor Antagonist BI1026706 Does Not Reduce Central Retinal Thickness in Center-Involved Diabetic Macular Edema.

Transl Vis Sci Technol 2020 03 30;9(4):25. Epub 2020 Mar 30.

Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany.

Purpose: The bradykinin 1 receptor may be important in inflammatory retinal vascular leakage in diabetic macular edema. BI 1026706 is an antagonist of bradykinin 1 receptor that has demonstrated efficacy in preclinical studies. Boehringer Ingelheim trial 1320.22 (NCT02732951) was a randomized, double-blind, placebo-controlled study. The pharmacodynamics, safety, and tolerability of oral BI 1026706 for 12 weeks were evaluated in patients with type 1 or type 2 diabetes mellitus and mild visual impairment owing to center-involved diabetic macular edema.

Methods: Patients ( = 105) were randomized to receive either oral BI 1026706 100 mg twice daily (morning and evening) or placebo for 12 weeks. The primary end point of the study was week 12 change from baseline in central subfield foveal thickness (CSFT) by spectral domain optical coherence tomography. Additional end points included absolute CSFT values, safety, and pharmacokinetics.

Results: After 12 weeks of treatment, there was no meaningful change from baseline in the adjusted mean CSFT in either treatment group (BI 1026706, 10.3 µm; placebo, -6.2 µm; adjusted mean treatment difference, 16.5 µm [95% confidence interval, -16.2 to 49.1]). There were also no differences in best-corrected visual acuity outcomes between treatment groups. Most reported adverse events were of mild or moderate intensity, and were balanced between treatment groups.

Conclusions: BI 1026706 was not superior to placebo in CSFT week-12 change from baseline. Therefore, BI 1026706 does not reduce CSFT, a morphologic sign of diabetic macular edema.

Translational Relevance: Kinin-kallikrein inhibition effects may not be apparent over 12 weeks for bradykinin 1 receptor inhibition alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/tvst.9.4.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396196PMC
March 2020

Preoperative Optical Coherence Tomography Findings of Foveal Splitting Rhegmatogenous Retinal Detachment.

Ophthalmologica 2020 Aug 7. Epub 2020 Aug 7.

To assess preoperative optical coherence tomography (OCT) findings of foveal splitting retinal detachment (RD), and to determine their postoperative outcomes. Consecutive patients who underwent RD surgery over a one-year period were included. Patients diagnosed with a detachment extending to the edge of the fovea on fundus examination (i.e. macula-On/Off) underwent macular OCT scanning. One-year visual acuity (VA) of macula-On/Off, macula-On and macula-Off eyes was compared. 85 eyes were included, of which 8 had a macula-On/Off RD. On preoperative OCT, all macula-On/Off RD had a foveal detachment extending beyond the foveal center, over a median distance of 632 µm. Mean VA of macula-On/Off eyes improved from 20/160 to 20/40 at one year postoperatively (p=0.035). Preoperative VA of macula-On/Off eyes was significantly better than macula-Off eyes (p=0.032) and lower than macula-On eyes (p=0.004). At one year, VA of macula-On/Off eyes was not different from macula-On eyes (p=0.320), and tend to be better than macula-Off eyes (p=0.062). Preoperative OCT revealed a shallow RD extending beyond the foveal center in eyes with clinical foveal splitting RD. These eyes called macula-On/Off RD had preopoerative VA between macula-On and macula-Off eyes, while their final VA was close to those with macula-On RD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000510726DOI Listing
August 2020

HAWK and HARRIER: Ninety-Six-Week Outcomes from the Phase 3 Trials of Brolucizumab for Neovascular Age-Related Macular Degeneration.

Ophthalmology 2021 01 20;128(1):89-99. Epub 2020 Jun 20.

University of Bonn, Bonn, Germany.

Purpose: To report the 96-week outcomes from HAWK and HARRIER.

Design: Phase 3, prospective, randomized, double-masked, multicenter studies comparing efficacy and safety of brolucizumab 3 mg (HAWK only) and 6 mg with aflibercept 2 mg in eyes with neovascular age-related macular degeneration (nAMD).

Participants: Treatment-naïve eyes with nAMD were randomized 1:1:1 to brolucizumab 3 mg (n = 358), brolucizumab 6 mg (n = 360), aflibercept 2 mg (n = 360; HAWK) or 1:1 to brolucizumab 6 mg (n = 370), aflibercept 2 mg (n = 369; HARRIER).

Methods: After 3 monthly loading doses, brolucizumab patients received every (q)-12-week (w) dosing, possibly adjusting to q8w dosing if disease activity was present at predefined disease activity assessment (DAA) visits. Aflibercept was dosed in a fixed q8w regimen. Visual and anatomic parameters were assessed throughout. Primary end point was at week 48 (48w), confirmed at 96w.

Main Outcome Measures: Mean best-corrected visual acuity (BCVA) change from baseline, proportion of patients on an q12w regimen, retinal thickness, retinal fluid changes, and safety, all to 96w.

Results: Mean change (least squares [LS] mean ± standard error) in BCVA from baseline to 96w in HAWK was 5.6±0.79 Early Treatment Diabetic Retinopathy Study (ETDRS) letters for brolucizumab 3 mg, 5.90±0.78 letters for brolucizumab 6 mg, and 5.3±0.78 letters for aflibercept and in HARRIER was 6.1±0.73 letters for brolucizumab 6 mg and 6.6 ± 0.73 letters for aflibercept. Greater central subfield thickness reductions were observed with brolucizumab 6 mg versus aflibercept in HAWK (LS mean, -174.8 μm vs. -148.7 μm; 95% confidence interval for treatment difference, -46.2 to -5.9 μm; P = 0.0115) and HARRIER (LS mean, -197.7 μm vs. -155.1 μm; 95% confidence interval for treatment difference, -62.0 to -23.3 μm; P < 0.0001). The proportions of eyes with intraretinal fluid and/or subretinal fluid (IRF/SRF) at 96w in HAWK were 31% (P = 0.0688) and 24% (P = 0.0002) for brolucizumab 3 mg and 6 mg and 37% for aflibercept, whereas in HARRIER, they were 24% for brolucizumab 6 mg (P < 0.0001) and 39% for aflibercept. At 92w (last DAA), a 45.4% and 38.6% probability was observed for brolucizumab 6 mg patients of maintaining an q12w treatment regimen in HAWK and HARRIER, respectively. Brolucizumab exhibited an overall well-tolerated safety profile.

Conclusions: Visual outcomes from 48w to 96w confirm the efficacy achieved at 48w. Brolucizumab demonstrated greater fluid resolution compared with aflibercept. The q12w potential for brolucizumab observed at 48w was maintained to 96w.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ophtha.2020.06.028DOI Listing
January 2021

Ten-year incidence and assessment of safe screening intervals for diabetic retinopathy: the OPHDIAT study.

Br J Ophthalmol 2021 Mar 10;105(3):432-439. Epub 2020 Jun 10.

Ophthalmology Department, Assistance Publique des Hôpitaux de Paris, Paris, France.

Background: To estimate the 10-year incidence of referable diabetic retinopathy (DR) in a French population with type 1 and 2 diabetes mellitus (DM). A secondary objective was the assessment of safe screening intervals in patients with diabetes without retinopathy.

Methods: Observational, prospective and multicentric study between June 2004 and September 2017 based on a regional screening programme for DR in the Paris region. The incidence of referable DR in patients without retinopathy at baseline was calculated by the Turnbull survival estimator. A safe screening interval was defined as a 95% probability of remaining without referable DR.

Results: Among the 25 745 participants with type 1 (n=6086) or type 2 (n=19 659) DM, the 10-year cumulative incidence of referable DR was 19.10% (95% CI 17.21% to 21.14%) and 17.03% (15.78% to 18.35%), median (IQR) follow-up=3.33 (4.24) years. The safe screening interval for patients without DR at the first examination for type 1 and 2 DM was 2.2 (95% CI 2.0 to 2.4) and 3.0 (2.9 to 3.1) years, respectively. In a subgroup of low-risk patients with type 2 DM, the safe screening interval was 4.2 (3.8 to 4.6) years.

Conclusions: These data suggest that in Paris area, a 2-year, 3-year and 4-year screening interval was considered safe for type 1 DM, type 2 DM and for low-risk patients with type 2 DM, respectively, without DR at the first examination. While these data might be used to support the consideration of extending screening intervals, a randomised clinical trial would be suitable to confirm the safety for patients with DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bjophthalmol-2020-316030DOI Listing
March 2021

Does internal limiting membrane peeling during epiretinal membrane surgery induce microscotomas on microperimetry? Study protocol for PEELING, a randomized controlled clinical trial.

Trials 2020 Jun 8;21(1):500. Epub 2020 Jun 8.

Department of Ophthalmology, CHU Nantes, Nantes, France.

Background: The epiretinal membrane (ERM) is a degenerative condition associated with age, which can cause loss of vision and/or metamorphopsia. The treatment of symptomatic ERM involves surgical removal including a vitrectomy followed by peeling of the ERM using a microforceps. As the internal limiting membrane (ILM) is adherent to the ERM, it is sometimes removed with it (spontaneous peeling). If ILM remains in place, it can be removed to reduce ERM recurrence. However, it is important to clarify the safety of ILM peeling, while it increases surgical risks and cause histological disorganization of the retina that can lead to microscotomas, may be responsible for definitive visual discomfort.

Methods: PEELING is a prospective, randomized, controlled, single-blind, and multicentered trial with two parallel arms. This study investigates the benefit/risk ratio of active ILM peeling among individuals undergoing ERM surgery without spontaneous ILM peeling. Randomization is done in the operating room after ERM removal if ILM remains in place. After randomization, the two groups-"active peeling of the ILM" and "no peeling of the ILM"-are compared during a total of three follow-up visits scheduled at month 1, month 6, and month 12. Primary endpoint is the difference in microscotomas before surgery and 6 months after surgery. Patients with spontaneous peeling are not randomized and are included in the ancillary study with the same follow-up visits and the same examinations as the principal study. Relevant inclusion criteria involve individuals aged > 18 years living with idiopathic symptomatic ERM, including pseudophakic patients with transparent posterior capsule or open capsule or lensed patients with age-related cataracts. The calculated sample size corresponds to 53 randomized eyes (one eye/patient) per arm that means 106 randomized eyes (106 randomized patients) in total and a maximum of 222 included patients (116 spontaneous peeling).

Discussion: ILM peeling is often practiced in ERM surgery to reduce ERM recurrence. It does not impair postoperative visual acuity, but it increases the surgical risks and causes anatomical damages. If active ILM peeling is significantly associated with more microscotomas, it may contraindicate the ILM peeling during primitive idiopathic ERM surgery.

Trial Registration: ClinicalTrials.gov, NCT02146144. Registered on 22 May 2014. Recruitment is still ongoing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13063-020-04433-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278143PMC
June 2020

Cluster of chalazia in nurses using eye protection while caring for critically ill patients with COVID-19 in intensive care.

Occup Environ Med 2020 08 28;77(8):584-585. Epub 2020 May 28.

Department of Ophtalmology, Lariboisière Hospital, University of Paris, Paris, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/oemed-2020-106677DOI Listing
August 2020

Reply.

Ophthalmology 2020 05;127(5):e34-e35

Université; de Paris, Ophthalmology Department, AP-HP, Hôpital Lariboisière, Paris, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ophtha.2020.01.002DOI Listing
May 2020

Topographic Variations of Choroidal Thickness in Healthy Eyes on Swept-Source Optical Coherence Tomography.

Invest Ophthalmol Vis Sci 2020 03;61(3):38

,.

Purpose: To assess topographic variations of choroidal thickness (CT) in the fovea and beyond in healthy eyes.

Methods: This cross-sectional study included healthy subjects ≤ 55 years of age with axial lengths (22-26 mm) and refractive error margins (-4D, +4D) in normal ranges. Images were acquired using swept-source optical coherence tomography angiography (OCT-A). Corneal thickness (CT) maps from 12 × 12-mm radial scans and 9 × 9-mm OCT-A B-scans were analyzed.

Results: The study included 64 eyes of 33 subjects (mean age, 37 years). Mean CT was >300 µm in all locations except the nasal outer macula. The subfoveal CT was >395 µm in 30% of cases; in 38.7% of cases, >50% of the CT map was thicker than 395 µm. The mean thickest choroidal point was 395.2 µm (range, 164-548 µm), located superior and temporal to the macula in 72.2% of cases and subfoveally in 1.8% of cases. The CT pattern was symmetrical (58%) or asymmetrical (42%) along a horizontal axis correlating with choroidal vein distribution. Half of the asymmetrical patterns were thicker in the inferior quadrants, with an oblique temporal watershed of venous drainage, and the other half were thicker superiorly. The mean vascularity index was ∼75% regardless of the mean CT.

Conclusions: One-third of healthy eyes of patients younger than age 55 had a thick choroid (>395 µm). In these normal eyes, the thickest choroidal point was not subfoveal, CT symmetry above and below the fovea depended on choroidal vein distribution, and choroidal vascularity index was independent from CT. No patients demonstrated fundus autofluorescence abnormalities, and the choriocapillaris remained visible even in thick choroids. These features could be interesting when differentiating normal versus pathological states.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1167/iovs.61.3.38DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401446PMC
March 2020

Optical coherence tomography-based consensus definition for lamellar macular hole.

Br J Ophthalmol 2020 12 27;104(12):1741-1747. Epub 2020 Feb 27.

Ophthalmology, Lariboisière Hospital, Paris, France.

Background: A consensus on an optical coherence tomography definition of lamellar macular hole (LMH) and similar conditions is needed.

Methods: The panel reviewed relevant peer-reviewed literature to reach an accord on LMH definition and to differentiate LMH from other similar conditions.

Results: The panel reached a consensus on the definition of three clinical entities: LMH, epiretinal membrane (ERM) foveoschisis and macular pseudohole (MPH). LMH definition is based on three mandatory criteria and three optional anatomical features. The three mandatory criteria are the presence of irregular foveal contour, the presence of a foveal cavity with undermined edges and the apparent loss of foveal tissue. Optional anatomical features include the presence of epiretinal proliferation, the presence of a central foveal bump and the disruption of the ellipsoid zone. ERM foveoschisis definition is based on two mandatory criteria: the presence of ERM and the presence of schisis at the level of Henle's fibre layer. Three optional anatomical features can also be present: the presence of microcystoid spaces in the inner nuclear layer (INL), an increase of retinal thickness and the presence of retinal wrinkling. MPH definition is based on three mandatory criteria and two optional anatomical features. Mandatory criteria include the presence of a foveal sparing ERM, the presence of a steepened foveal profile and an increased central retinal thickness. Optional anatomical features are the presence of microcystoid spaces in the INL and a normal retinal thickness.

Conclusions: The use of the proposed definitions may provide uniform language for clinicians and future research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bjophthalmol-2019-315432DOI Listing
December 2020

Time to Call into Question the Fundus-based Evaluation of Diabetic Retinopathy after Intravitreal Injections.

Authors:
Ramin Tadayoni

J Ophthalmic Vis Res 2020 Jan-Mar;15(1):4-6. Epub 2020 Feb 2.

Université de Paris, Ophthalmology Department, AP-HP, Hôpital Lariboisière, F-75010, Paris, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18502/jovr.v15i1.5971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001029PMC
February 2020

Retinal Capillary Plexus Pattern and Density from Fovea to Periphery Measured in Healthy Eyes with Swept-Source Optical Coherence Tomography Angiography.

Sci Rep 2020 01 30;10(1):1474. Epub 2020 Jan 30.

Université de Paris, Ophthalmology Department, AP-HP, Hôpital Lariboisière, F-75010, Paris, France.

Optical coherence tomography angiography is evolving towards wider fields of view. As single widefield acquisitions have a lower resolution, preventing an accurate segmentation of vascular plexuses in the periphery, we examined the retinal vascularisation from the macula to the periphery in all retinal quadrants, using 3 × 3-mm volume scans, to obtain montages with sufficient image resolution up to 11 mm from the foveal centre. Images were qualitatively and quantitatively analysed, using C- and B-scan approaches to calculate the capillary density (CD) and the interplexus distance (IPD). Three vascular plexuses (i.e., superficial vascular plexus: SVP, intermediate capillary plexus: ICP, and deep capillary plexus: DCP) were observed up to the mid-periphery in all sectors. The CD of the SVP decreased from about 5 mm of eccentricity, along with ganglion cell density decrease. The CD of the ICP progressively decreased from the fovea towards the periphery, along with the retinal thinning and then vanished from 8 to 9 mm of eccentricity, becoming undetectable beyond. This ICP disappearance resulted in an increased IPD between the SVP and the DCP in an area known to be frequently affected by capillary drop-out in diabetic retinopathy. The DCP only showed a slightly decreased CD towards the retinal periphery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-58359-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992636PMC
January 2020

IL-1β induces rod degeneration through the disruption of retinal glutamate homeostasis.

J Neuroinflammation 2020 Jan 3;17(1). Epub 2020 Jan 3.

Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012, Paris, France.

Background: Age-related macular degeneration is characterized by the accumulation of subretinal macrophages and the degeneration of cones, but mainly of rods. We have previously shown that Mononuclear Phagocytes-derived IL-1β induces rod photoreceptor cell death during experimental subretinal inflammation and in retinal explants exposed to IL-1β but the mechanism is unknown.

Methods: Retinal explants were culture in the presence of human monocytes or IL-1β and photoreceptor cell survival was analyzed by TUNEL labeling. Glutamate concentration and transcription levels of gene involved in the homeostasis of glutamate were analyzed in cell fractions of explant cultured or not in the presence of IL-1β. Glutamate receptor antagonists were evaluated for their ability to reduce photoreceptor cell death in the presence of IL1-β or monocytes.

Results: We here show that IL-1β does not induce death in isolated photoreceptors, suggesting an indirect effect. We demonstrate that IL-1β leads to glutamate-induced rod photoreceptor cell death as it increases the extracellular glutamate concentrations in the retina through the inhibition of its conversion to glutamine in Müller cells, increased release from Müller cells, and diminished reuptake. The inhibition of non-NMDA receptors completely and efficiently prevented rod apoptosis in retinal explants cultured in the presence of IL-1β or, more importantly, in vivo, in a model of subretinal inflammation.

Conclusions: Our study emphasizes the importance of inflammation in the deregulation of glutamate homeostasis and provides a comprehensive mechanism of action for IL-1β-induced rod degeneration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12974-019-1655-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942287PMC
January 2020