Photocoagulation or sham laser in addition to conventional anti-VEGF therapy in macular edema associated with TelCaps due to diabetic macular edema or retinal vein occlusion (TalaDME): a study protocol for a multicentric, French, two-group, non-commercial, active-control, observer-masked, non-inferiority, randomized controlled clinical trial.

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.

In vivo confocal microscopic study of corneal innervation in Sjögren's Syndrome with or without small fiber neuropathy.

PURPOSE: To study changes in the subbasal nerve plexus by In vivo confocal microscopy (IVCM) in Sjögren's Syndrome (SS) with or without associated Small Fiber Neuropathy (SFN), in order to prevent diagnostic delay. METHODS: Seventy-one patients with SS, including 19 with associated SFN, 20 healthy volunteers and 20 patients with Meibomian gland dysfunction (MGD) were included in this retrospective case-control study. IVCM was used to investigate subbasal nerve plexus density and morphology. RESULTS: Corneal sensitivity as evaluated with the Cochet-Bonnet aesthesiometer was significantly reduced in the SS group versus the control group (P = 0.026) and the MGD group (P = 0.037). The number of inflammatory cells was significantly increased in the SS group to 86.2 ± 82.1 cells/mm2 compared to the control group (P < 0.001). The density of the subbasal nerve plexus was significantly reduced to 16.7 ± 6.5 mm/mm2 in the SS group compared to the control group (P < 0.005) and the MGD group (P = 0.042). The tortuosity of the nerves in the SS group was significantly increased compared to the control group (P < 0.001) and the MGD group (P = 0.025). The average number of subbasal nerve plexus neuromas was significantly increased in the SS group compared to the control group (P = 0.001), with a significant increase in the average number of neuromas in SS patients with associated SFN compared to SS patients without SFN (P = 0.008). CONCLUSION: IVCM can be useful to detect corneal nerve changes in SS patients and may allow earlier diagnosis of the disease and to consider new therapeutic approaches.

Intravitreal Dexamethasone in Diabetic Macular Oedema: A Way of Enhancing the Response to Anti-VEGF in Non- or Poor Responders?

BACKGROUND AND PURPOSE: The aim of this study was to describe the outcomes of a switch back to anti-vascular endothelial growth factor (VEGF) in diabetic macular oedema (DME) eyes treated temporarily with a dexamethasone implant (DEXi), after an initial poor response to anti-VEGF. METHODS: The study involved a case series. RESULTS: Twenty-three eyes of 17 patients were included. All were poorly responsive to anti-VEGF and switched to a DEXi after a mean of 12 anti-VEGF injections. The mean best-corrected visual acuity (BCVA) increased from 0.25 ± 0.19 (decimals) to 0.29 ± 0.20 after switching to the DEXi (p = 0.11). BCVA remained stable (0.31 ± 0.23; p = 0.11) after switching back to anti-VEGF, one month after the last injection. The mean central macular thickness (CMT) decreased significantly from 517.0 ± 128.5 µm to 343.4 ± 118.9 µm (p < 0.001) after switching to the DEXi. In eyes receiving ≥3 anti-VEGF injections during the switch back, the CMT 1 month after the last anti-VEGF injection was significantly decreased compared to the CMT before the switch to the DEXi (mean change of - 95.55 ± 89.82 µm, p = 0.005). CONCLUSION: Switching back poorly responsive DME eyes to anti-VEGF after temporary DEXi therapy is associated with good anatomical and visual outcomes similar to those obtained with the DEXi, provided that at least 3 anti-VEGF injections are administered. The DEXi might restore retinal sensitivity to anti-VEGF.

Expectations and fears of patients with diabetes and macular edema treated by intravitreal injections.

AIMS: Clinical outcomes of diabetic macular edema (DME) have been widely described, but data on diabetic retinopathy perceptions by diabetes patients are limited. The aim of this survey was to explore the lived experience, knowledge, fears and expectations about disease, and treatment in patients with diabetes and macular edema treated with intravitreal injections (IVTI) and to characterize patient profiles. METHODS: Cross-sectional survey including a preliminary qualitative phase (20 patients with DME, treated or treatment-naive, 5 female and 15 male, age 36-74 years) followed by a quantitative survey (116 patients treated with IVTI for DME). Data ASKIA Analyze (version 5.3.3.5) was used for descriptive statistics, and R software (version 3.4.1) for multiple correspondence analysis. RESULTS: The qualitative phase identified the wording used by patients and information helpful to propose modalities of response in the quantitative phase. In the quantitative survey (116 patients, mean age 66.6 years), most patients were treated with anti-vascular endothelial growth factor. Overall, 71.9% reported that the disease negatively affected their daily activities and 33.1% considered that regular visits to the ophthalmologist were disrupting their life. Treatment expectations differed significantly between patients in terms of disease experience (visit and injection schedules), fears and feelings, and relationship with physicians, allowing three patient profiles to be identified: "Worried" patients (n = 45) felt isolated and were worried about the need for repeated treatment and possible side effects. They were mainly active men aged < 60 with type I diabetes (T1D) and DME diagnosed for > 2 years; "Curious" patients (n = 21) experienced insufficient support and requested more information on their disease and existing treatments. They were mainly single women aged 60-69 years; "Passive" patients (n = 50) felt sufficiently informed by their ophthalmologist and were not concerned by DME. They were older (mean age: 70 years) and mainly type 2 diabetic men. CONCLUSIONS: Patients with diabetes and macular edema treated with IVTI form a heterogeneous group regarding fears and expectations. Different patient profiles were identified and need to be confirmed in larger studies. A better understanding of psychological profiles may optimize compliance of diabetic patients.

Indocyanine green angiography for identifying telangiectatic capillaries in diabetic macular oedema.

AIMS: During diabetic macular oedema (DME), a spectrum of capillary abnormalities is commonly observed, ranging from microaneurysms to large microvascular abnormalities. Clinical evidence suggests that targeted photocoagulation of large microvascular abnormalities may be beneficial, but their detection is not done in a routine fashion. It was reported that they are better identified by indocyanine green angiography (ICGA) than by fluorescein angiography. Here, we investigated the prevalence and ICGA and optical coherence tomography (OCT) features of retinal microvascular abnormalities in a group of patients with DME. METHODS: Observational study. The fundus photographs, ICGA and structural and angiographic OCT charts of 35 eyes from 25 consecutive patients with DME were reviewed. RESULTS: 22 eyes (63%) had at least one focal area of microvascular abnormalities showing prolonged indocyanine green (ICG) staining (ie, beyond 10 mins after injection). In particular, all eyes (n=9) with circinate hard exudates showed foci of late ICG staining. These areas were either isolated globular capillary ecstasies or a cluster of ill-defined capillary abnormalities. They were located at a median distance of 2708 µm from the fovea (range: 1064-4583 µm). Their diameter ranged from 153 to 307 µm. During ICGA, 91% showed increased their contrast and apparent size in late frames, whereas 79% of microaneurysms showed reduced contrast on late frames. OCT angiography was not contributive for the detection of these lesions. CONCLUSION: Late ICG staining revealing large microvascular abnormalities is commonly observed during DME. Because of their specific angiographic and OCT features relative to microaneurysms, we propose to name them telangiectatic capillaries (TelCaps).

Glucagon-like Peptide 1 Receptor Agonists, Diabetic Retinopathy and Angiogenesis: The AngioSafe Type 2 Diabetes Study.

AIMS: Recent trials provide conflicting results on the association between glucagon-like peptide 1 receptor agonists (GLP-1RA) and diabetic retinopathy (DR). The aim of the AngioSafe type 2 diabetes (T2D) study was to determine the role of GLP-1RA in angiogenesis using clinical and preclinical models. METHODS: We performed two studies in humans. In study 1, we investigated the effect of GLP-1RA exposure from T2D diagnosis on the severity of DR, as diagnosed with retinal imaging (fundus photography). In study 2, a randomized 4-week trial, we assessed the effect of liraglutide on circulating hematopoietic progenitor cells (HPCs), and angio-miRNAs.We then studied the experimental effect of Exendin-4, on key steps of angiogenesis: in vitro on human endothelial cell proliferation, survival and three-dimensional vascular morphogenesis; and in vivo on ischemia-induced neovascularization of the retina in mice. RESULTS: In the cohort of 3154 T2D patients, 10% displayed severe DR. In multivariate analysis, sex, disease duration, glycated hemoglobin (HbA1c), micro- and macroangiopathy, insulin therapy and hypertension remained strongly associated with severe DR, while no association was found with GLP-1RA exposure (o 1.139 [0.800-1.622], P = .47). We further showed no effect of liraglutide on HPCs, and angio-miRNAs. In vitro, we demonstrated that exendin-4 had no effect on proliferation and survival of human endothelial cells, no effect on total length and number of capillaries. Finally, in vivo, we showed that exendin-4 did not exert any negative effect on retinal neovascularization. CONCLUSIONS: The AngioSafe T2D studies provide experimental and clinical data confirming no effect of GLP-1RA on angiogenesis and no association between GLP-1 exposure and severe DR.

Widefield OCT-Angiography and Fluorescein Angiography Assessments of Nonperfusion in Diabetic Retinopathy and Edema Treated with Anti-Vascular Endothelial Growth Factor.

PURPOSE: To assess change in retinal nonperfusion (NP) after anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) using 2 different imaging modalities: swept-source widefield (SS-WF) OCT angiography (OCTA) and ultra-widefield (UWF) fluorescein angiography (FA). DESIGN: Observational case series. PARTICIPANTS: Ten eyes of 9 patients with severe nonproliferative diabetic retinopathy (NPDR) or proliferative DR (PDR) initiating 3 monthly anti-VEGF intravitreal injections for DME. METHODS: All eyes were imaged with UWF color fundus photographs (CFPs), UWF FA, and SS-WF OCTA at baseline (M0) and 1 month after the third anti-VEGF injection (M3). All images were aligned and divided into 16 boxes for analysis of NP areas by 2 blinded retina specialists. MAIN OUTCOME MEASURES: The number of discrepancies between SS-WF OCTA and UWF FA regarding the detection of NP areas and small vessels passing through NP areas; assessment of DR severity on UWF CFP; and change in each NP area between M0 and M3: number of boxes/eye with presence of at least 1 NP area, number of arterioles or venules that disappeared or reappeared, and number of NP areas in which capillaries disappeared or reappeared. RESULTS: The diabetic retinopathy (DR) severity score improved by at least 1 stage in 8 of 10 eyes, with a significant decrease in the mean number of microaneurysms and retinal hemorrhages on UWF CFP at M3 versus M0 (n = 40±28 vs. 121±57; P = 0.0020) and regression of fundus neovascularization when present. All NP areas detected on FA were seen on SS-WF OCTA, but additional NP areas were detected on SS-WF OCTA at M0 in 29% (46/160) of boxes. No reperfusion of arterioles or venules was observed at M3 on FA or SS-WF OCTA. Retinal capillaries were only visible on OCTA, and no reperfusion in NP areas was observed even when a reduction in dark areas was visible on FA. CONCLUSIONS: No reperfusion of vessels or capillary network was detected in NP areas using 2 imaging techniques, UWF FA and SS-WF OCTA, in eyes with DR after 3 anti-VEGF injections. The detection rate of NP areas was higher with SS-WF OCTA than with UWF FA.

ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY CAN IMPROVE DIABETIC RETINOPATHY SCORE WITHOUT CHANGE IN RETINAL PERFUSION.

PURPOSE: To compare the changes in retinal perfusion on ultra-wide-field fluorescein angiography with the changes in diabetic retinopathy lesions observed on ultra-wide-field fundus color photographs after 3 monthly anti-vascular endothelial growth factor injections. METHODS: Retrospective interventional cohort study analyzing the files of 14 patients with DR (18 eyes). UWF color photos and FA were analyzed at baseline (M0) and 1 month after the third anti-VEGF injection (M3). The main outcomes included the count of the number of red dots (microaneurysms, hemorrhages) and assessment of DR severity score (DRSS); the analysis of non-perfusion areas and disappearance or reappearance of arterioles or venules in the non-perfusion areas on FA. RESULTS: Eighteen eyes of 14 diabetic patients, with mean age of 63 ± 5 years, were included. The DRSS score improved by at least one stage in 11/18 (61%) eyes. The mean number of red dots significantly decreased at M3 (n = 80 ± 85) compared with M0 (n = 139 ± 130) (P < 0.0001). No reperfusion of arterioles or venules was observed in or around nonperfusion areas. CONCLUSION: After anti-vascular endothelial growth factor injections, the improvement in the DRSS score based on color fundus photographs can occur without retinal reperfusion on ultra-wide-field fluorescein angiography.

Association Between Vessel Density and Visual Acuity in Patients With Diabetic Retinopathy and Poorly Controlled Type 1 Diabetes.

Importance: Capillary dropout is a hallmark of diabetic retinopathy, but its role in visual loss remains unclear. Objective: To examine how macular vessel density is correlated with visual acuity (VA) in patients younger than 40 years who have type 1 diabetes without macular edema but who have diabetic retinopathy requiring panretinal photocoagulation. Design, Settings, and Participants: Retrospective cohort study of VA and optical coherence tomography angiography data collected from consecutive patients during a single visit to Lariboisière Hospital, a tertiary referral center in Paris, France. The cohort included 22 eyes of 22 patients with type 1 diabetes without macular edema but with bilateral rapidly progressive diabetic retinopathy that was treated with panretinal photocoagulation between August 15, 2015, and December 30, 2016. Eyes were classified into 2 groups by VA: normal (logMAR, 0; Snellen equivalent, 20/20) and decreased (logMAR, >0; Snellen equivalent, <20/20). The control group included 12 eyes from age-matched healthy participants with normal vision. Main Outcomes and Measures: Visual acuity and mean vessel density in 4 retinal vascular plexuses: the superficial vascular plexus and the deep capillary complex, which comprises the intermediate capillary plexus and the deep capillary plexus. Results: Of the 22 participants, 11 (50%) were men, mean (SD) age was 30 (6) years, and mean (SD) hemoglobin A1c level was 8.9% (1.6%). Of the 22 eyes with diabetic retinopathy, 13 (59%) had normal VA and 9 (41%) had decreased VA (mean [SD]: logMAR, 0.12 [0.04]; Snellen equivalent, 20/25). Mean [SE] vessel density was lower for eyes with diabetic retinopathy and normal VA compared with the control group in the superficial vascular plexus (44.1% [0.9%] vs 49.1% [0.9%]; difference, -5.0% [1.3%]; 95% CI, -7.5% to -2.4%; P < .001), in the deep capillary complex (44.3% [1.2%] vs 50.6% [1.3%]; difference, -6.3% [1.8%]; 95% CI, -9.9% to -2.7%; P = .001), in the intermediate capillary plexus (43.8% [1.2%] vs 49.3% [1.2%]; difference, -5.5% [1.7%]; 95% CI, -9.0% to -2.0%; P = .003), and in the deep capillary plexus (24.5% [1.0%] vs 30.5% [1.0%]; difference, -6.1% [1.4%]; 95% CI, -8.9% to -3.2%; P < .001). Mean vessel density was lower in eyes with diabetic retinopathy and decreased VA compared with eyes with diabetic retinopathy and normal VA; the mean (SE) loss was more pronounced in the deep capillary complex (34.6% [1.5%] vs 44.3% [1.2%]; difference, -9.6% [1.9%]; 95% CI, -13.6% to -5.7%; P < .001), especially in the deep capillary plexus (15.2% [1.2%] vs 24.5% [1.0%]; difference, -9.3% [1.5%]; 95% CI, -12.4% to -6.1%; P < .001), than in the superficial vascular plexus (39.6% [1.1%] vs 44.1% [0.9%]; difference, -4.5% [1.4%]; 95% CI, -7.3% to -1.7%; P = .002). Conclusions and Relevance: These data suggest that in patients with type 1 diabetes without macular edema but with severe nonproliferative or proliferative diabetic retinopathy, decreased VA may be associated with the degree of capillary loss in the deep capillary complex.

BENEFIT OF INTRAOPERATIVE OPTICAL COHERENCE TOMOGRAPHY FOR VITREOMACULAR SURGERY IN HIGHLY MYOPIC EYES.

PURPOSE: To report the feasibility and information provided by intraoperative optical coherence tomography (iOCT) during vitreomacular surgery in highly myopic eyes. METHODS: Retrospective observational case series on consecutive highly myopic eyes that underwent vitreomacular surgery with iOCT for epiretinal membrane (ERM), macular hole, and myopic foveoschisis. The main outcome was the qualitative and quantitative assessment of retinal changes: detection of persistent epiretinal structures, new openings, central macular thickness, and macular hole diameters after each step of the surgical procedure. Quantitative measurements (in pixels) were manually obtained on iOCT video screen captures. RESULTS: Twenty-two eyes were included: six ERMs, 10 macular holes, and 6 with myopic foveoschisis. An unsuspected postpeeling macular opening was detected by iOCT in 2/22 eyes. Intraoperative optical coherence tomography also allowed for detecting the presence of residual fragments of the vitreous cortex in 6/12 eyes after surgically induced posterior vitreous detachment. Intraoperative optical coherence tomography detected residual fragments of the internal limiting membrane in 5/21 eyes after internal limiting membrane peeling, and residual fragments of ERM in 3/15 eyes with ERM. Quantitative analysis did not find any significant change in central macular thickness and macular hole diameters before and after ERM and internal limiting membrane peeling. CONCLUSION: In highly myopic eyes, iOCT could help assess undetected macular openings and otherwise posterior vitreous status and epiretinal structure peeling.

Comparing Parafoveal Cone Photoreceptor Mosaic Metrics in Younger and Older Age Groups Using an Adaptive Optics Retinal Camera.

BACKGROUND AND OBJECTIVE: To analyze cone mosaic metrics on adaptive optics (AO) images as a function of retinal eccentricity in two different age groups using a commercial flood illumination AO device. PATIENTS AND METHODS: Fifty-three eyes of 28 healthy subjects divided into two age groups were imaged using an AO flood-illumination camera (rtx1; Imagine Eyes, Orsay, France). A 16° × 4° field was obtained horizontally. Cone-packing metrics were determined in five neighboring 50 µm × 50 µm regions. Both retinal (cones/mm2 and µm) and visual (cones/degrees2 and arcmin) units were computed. RESULTS: Results for cone mosaic metrics at 2°, 2.5°, 3°, 4°, and 5° eccentricity were compatible with previous AO scanning laser ophthalmoscopy and histology data. No significant difference was observed between the two age groups. CONCLUSIONS: The rtx1 camera enabled reproducible measurements of cone-packing metrics across the extrafoveal retina. These findings may contribute to the development of normative data and act as a reference for future research. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:45-50.].

Indocyanine-green-guided targeted laser photocoagulation of capillary macroaneurysms in macular oedema: a pilot study.

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.

CORRELATION BETWEEN CYSTOID SPACES IN CHRONIC DIABETIC MACULAR EDEMA AND CAPILLARY NONPERFUSION DETECTED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To study the relationship between the location of cystoid spaces and retinal capillary nonperfusion areas in diabetic cystoid macular edema (DCME). METHODS: In this retrospective study, 24 eyes of 21 patients with chronic DCME were followed using optical coherence tomography angiography. The capillary density of the superficial capillary plexus and deep capillary plexus was measured using AngioAnalytics software in all DCME eyes and in 20 healthy controls. Diabetic cystoid macular edema improved spontaneously or after treatment in 11 eyes. RESULTS: The intraretinal cystoid spaces were surrounded by capillary-flow void areas in the superficial capillary plexus in 71% of cases and in the deep capillary plexus in 96% of cases. The deep capillary plexus had lost its regular pattern in all cases. The capillary density was decreased in both plexus (mean decrease of -23.0% in the superficial capillary plexus and -12.4% in the deep capillary plexus vs. normal). In the 11 cases with DCME resolution, the capillary did not reperfuse in areas of resolved cystoid spaces, and the capillary density did not change significantly. CONCLUSION: In chronic DCME, cystoid spaces were located within capillary dropout areas. No reperfusion occurred after DCME resolution. The impact of the severity of this nonperfusion on the risk of recurrence of DCME remains to be clarified.

Potential Role of In Vivo Confocal Microscopy for Imaging Corneal Nerves in Transthyretin Familial Amyloid Polyneuropathy.

IMPORTANCE: Small fiber neuropathy (SFN) is an important feature of transthyretin familial amyloid polyneuropathy (TTR-FAP). A practical and objective method for the clinical evaluation of SFN is needed to improve the management of this disease. In vivo confocal microscopy (IVCM) of the corneal nerves, a rapid noninvasive technique, may be used as a surrogate marker of SFN. OBJECTIVE: To determine the correlation of SFN with IVCM in patients with TTR-FAP. DESIGN, SETTING, AND PARTICIPANTS: A prospective, single-center, cross-sectional controlled study was conducted at the French National Reference Center for TTR-FAP from June 1, 2013, to June 30, 2014. Fifteen patients with TTR-FAP underwent a complete neurologic examination, including Neuropathy Impairment Score of the Lower Limbs, hand grip strength, and evaluation of vegetative dysfunction, as well as electrophysiologic studies (nerve conduction and electrochemical skin conductance) and intraepidermal nerve fiber density quantification. Patients and 15 controls (matched for age and sex) underwent ophthalmologic assessments, including corneal esthesiometry and IVCM. MAIN OUTCOMES AND MEASURES: Correlation of corneal nerve fiber length (CNFL) with the severity of SFN. RESULTS: Of the 15 patients enrolled in the study, 6 were women (40%); mean (SD) age was 54.4 [13.7] years. The CNFL was shorter in the patients than in controls (13.08 vs 17.57 mm/mm2; difference of 4.49 [95% CI, 0.72 to 8.27]; P = .02). The patients' CNFL correlated with the severity of both autonomic neuropathy assessed by the Compound Autonomic Dysfunction Test (rs = 0.66 [95% CI, 0.22 to 0.87]; P = .008) or electrochemical skin conductance (rs = 0.80 [95% CI, 0.50 to 0.93]; P < .001) and sensorimotor neuropathy assessed using the Neuropathy Impairment Score of the Lower Limbs (rs = -0.58 [95% CI, -0.84 to -0.11]; P = .02). Patients with altered sensory nerve action potentials and intraepidermal nerve fiber density had a shorter CNFL (P = .04 and P = .02, respectively). The CNFL could be measured in all patients compared with sensory nerve action potentials (11 patients [73%; 95% CI, 44% to 92%]; P < .001) and intraepidermal nerve fiber density (4 patients [27%; 95% CI, 8% to 55%]; P < .001). CONCLUSIONS AND RELEVANCE: In these 15 patients with TTR-FAP, IVCM measurement permitted rapid, noninvasive evaluation of small-fiber alterations in patients and could be used to assess SFN in this setting. The CNFL could be measured in all patients, thus avoiding the floor effect seen with other neuropathy measures. Longitudinal studies with more cases evaluated are needed to define the place of IVCM in monitoring patients with TTR-FAP.

Symmetry in early response to intravitreal ranibizumab in bilateral diabetic macular oedema.

PURPOSE: To study the symmetry in response to bilateral diabetic macular oedema (DME) treated with bilateral intravitreal injections of ranibizumab (IVR). METHODS: The charts of 36 eyes of 18 patients treated with a loading dose of three monthly IVR in both eyes were retrospectively reviewed. Favourable anatomical response was defined as a decrease by more than 10% in baseline central macular thickness (CMT), and favourable functional response was defined as an increase in visual acuity (VA) ≥5 letters. A symmetric response was defined as a similar anatomical and/or functional response in the first (FE) and second (SE) treated eyes. RESULTS: The VA improved significantly after ranibizumab treatment in both eyes (p < 0.01). A statistically significant positive correlation was found for the functional response to ranibizumab between the FE and the SE (R(2)  = 0.26, p = 0.03). The mean CMT decreased significantly in both eyes (p < 0.01). A strong positive correlation was observed between the anatomical response to ranibizumab in the FE and the SE (R(2)  = 0.37, p = 0.01). Symmetric favourable anatomical and functional responses were observed in 13 patients (72%). In two additional patients, an asymmetric functional response was observed despite a decrease in retinal thickness in both eyes. CONCLUSION: Symmetric anatomical and functional responses were observed in 72% of patients with DME after three initial IVR in each eye. This finding could be of clinical interest in the decision to treat the fellow eye, in a disease where a bilateral involvement is frequent.

Evolution of Subfoveal Detachments Secondary to Idiopathic Epiretinal Membranes after Surgery.

PURPOSE: To study the characteristics of subfoveal abnormalities secondary to idiopathic epiretinal membranes (ERM) using improved-resolution spectral-domain optical coherence tomography (SD OCT) and their evolution after surgery. DESIGN: Retrospective, observational cohort study. PARTICIPANTS: The files of 344 patients operated on consecutively for ERM over a 2-year period in a single tertiary ophthalmologic center were reviewed. Patients with vitreomacular traction syndrome, secondary ERM, or both were excluded. METHODS: In all, 293 eyes with idiopathic ERM were included in the final analysis. Fundus photographs were reviewed to assess the presence of a yellow foveal spot, and SD OCT analysis was performed. MAIN OUTCOME MEASURES: Presence or absence of a subfoveal abnormality and its SD OCT characteristics before and after surgery at 1 month, 3 months, and at final visit; best-corrected visual acuity (BCVA) and central macular thickness at baseline, 1 month, 3 months, and at the final visit. RESULTS: Before surgery, a subfoveal detachment (SD) corresponding to the yellow deposit was present in 59 of 293 eyes (20%). No difference was found for the postoperative BCVA between the 59 eyes with SD before surgery and the 234 eyes without SD (0.253 ± 0.14 logarithm of the minimum angle of resolution [logMAR] vs. 0.262 ± 0.24 logMAR, respectively; P = 0.6). Sixty-eight percent (n = 40/59) of SD disappeared after surgery during a mean follow-up of 4.8 ± 3.2 months, most of them (62%) before month 3. Among eyes with preoperative SD, no difference was found for the postoperative BCVA between eyes with disappeared SD and those with persistent SD. CONCLUSIONS: Subfoveal detachments secondary to idiopathic ERM were observed in 20% of these eyes. They disappeared after surgery in more than two thirds of cases, usually early during postoperative course. Subfoveal detachments do not affect visual outcome and should not interfere with surgical decision making.

Efficacy of dexamethasone intravitreal implant for the treatment of diabetic macular edema.

PURPOSE: To assess the efficacy of a single dexamethasone intravitreal implant (Dex-I) injection for the treatment of diabetic macular edema (DME). METHODS: This was a retrospective chart review of 39 eyes (34 consecutive patients). Best-corrected visual acuity (BCVA), central macular thickness (CMT), and increase in intraocular pressure (IOP) (gt;24 mm Hg) were analyzed before treatment and 2 and 4 months after injection. RESULTS: Preoperative mean CMT was 559 ± 111 µm and decreased to 338 ± 84 and 477 ± 140 µm 2 and 4 months after injection, respectively. Although all eyes showed a significant decrease in CMT 2 months after injection (p<0.0001), a recurrence of the macular edema was observed 4 months after injection in 79% of eyes. Mean BCVA improvement (logMAR) was 0.13 ± 0.18 (p<0.0001) and 0.07 ± 0.21 (p = 0.049) 2 and 4 months after injection, respectively, without significant difference between vitrectomized and nonvitrectomized eyes. Eight eyes (21%) developed reversible increase in IOP 2 months after injection. CONCLUSIONS: Thirty percent of DME eyes had gained more than 2 logMAR lines 2 months after Dex-I injection and safety was good. Visual acuity gain was maintained 4 months after injection despite a recurrence of edema in most cases.

Correlation between ganglion cell layer thinning and poor visual function after resolution of diabetic macular edema.

PURPOSE: To assess the thickness of the ganglion cell-inner plexiform layer (GCIPL) in eyes with resolved diabetic macular edema (DME), using spectral-domain optical coherence tomography (SD-OCT), and its relationship with the visual function. METHODS: This retrospective observational case-control cohort study included eyes of diabetic patients with resolved DME (r-DME eyes), that is, normal central macular thickness (CMT) after treatment of DME, and eyes of aged-matched diabetic patients without maculopathy (no-DME eyes). The GCIPL thickness was measured on a macular cube SD-OCT scan using a specific automatic segmentation algorithm. Linear regression analyses were performed to determine the association between the GCIPL thickness and the visual acuity (VA) measured at the time of the OCT measurement. RESULTS: Average GCIPL thickness was reduced in r-DME eyes compared with no-DME eyes (74 ± 14 µm versus 83.2 ± 6 µm, P = 0.0189), whereas no significant difference in mean CMT was observed (260.0 ± 34 µm versus 265.7 ± 22 µm, P = 0.847). Visual acuity significantly correlated with the average GCIPL thickness (r = 0.8, P < 0.0001) and minimum GCIPL thickness (r = 0.84, P < 0.0001) in r-DME eyes. CONCLUSIONS: Despite favorable anatomic response and restoration of a CMT in the range of normal values after resolution of DME, the GCIPL thickness in r-DME eyes was lower than that in no-DME eyes and correlated with the VA. These results suggest that inner retinal alterations occurring in patients with DME and diabetic retinopathy may lead to visual deficiency persisting after treatment.

Surgical outcomes of florid diabetic retinopathy treated with antivascular endothelial growth factor.

PURPOSE: To evaluate the effectiveness of vitreoretinal surgery combined with antivascular endothelial growth factor therapy to treat florid diabetic retinopathy, a rare and severe form of diabetic retinopathy in young patients. METHODS: Retrospective observational case series including 61 eyes of 45 patients operated on for florid diabetic retinopathy over the past 5 years, with preoperative or intraoperative intravitreal injection of bevacizumab. Cases were classified into three stages of disease severity, according to the extension of the fibrovascular membranes. Main outcome measures were mean change in visual acuity, anatomical outcome, and surgical complications. RESULTS: After a mean follow-up of 20.3 months, the mean visual acuity significantly increased from +1.7 logMAR before surgery to +0.8 logMAR after surgery (P < 0.01). The visual gain was significant in Stages I and II (P < 0.05) but not significant in Stage III. A flat retina without silicone oil was achieved in 84% of eyes. Eight eyes (13%) progressed to neovascular glaucoma and/or phthisis despite repeated surgeries. CONCLUSION: Vitrectomy combined with antivascular endothelial growth factor therapy allows both favorable visual and anatomical outcomes in this rapidly evolving disease. Prognosis remains poor in severe stages, suggesting that the earlier the surgery performed, the better is the visual prognosis.

Influence of pulse pressure and spontaneous variations of macular thickness in patients with diabetic macular oedema.

PURPOSE: To study spontaneous variations of central macular thickness (CMT) and its relation to blood pressure (BP) in patients with diabetic macular oedema (DME). METHODS: 23 diabetic patients presenting with DME with a CMT ≥ 260 µm on optical coherence tomography (OCT-3, Carl Zeiss Meditec, CA) were followed every 2 weeks for 3 months. At baseline, ambulatory 24H-BP monitoring (ABPM) was performed, as well as five CMT measurements (9 am, 12 am, 3 pm, 6 pm and 9 am the day after). During follow-up, BP and CMT were simultaneously measured at 9 am. RESULTS: Significant spontaneous variations in CMT (at least one change in CMT greater than 11% compared to the median CMT value) were observed over 3 months in 48% of patients. Mean CMT decreased over the day and increased during the night, but not significantly (p = 0.1). During the 6 visits, the CMT at 9 am positively correlated with the pulse pressure (PP) measured at the same time (r = 0.29, p = 0.0008). In addition, the mean 24H-CMT was positively correlated with the mean 24H- PP (r = 0.48, p = 0.02). CONCLUSION: Significant spontaneous changes in CMT of patients with DME were observed in nearly half of cases over 3 months. Retinal thickness was correlated to PP levels (patients with higher CMT had higher PP levels). This high variability of macular oedema, and the influence of BP on retinal thickness, should be taken into consideration by practitioners when evaluating the benefit of a therapy in DME.