Switching to subtenon triamcinolone acetonide does not jeopardize the functional and anatomic outcomes of dexamethasone implant treated eyes with diabetic macular edema.

BACKGROUND: Intraocular dexamethasone implant (DEXi) is an efficient treatment for diabetic macular edema (DME). However, it may be unavailable or contraindicated. Triamcinolone acetonide is another corticosteroid that has proved to be safe and effective in treating macular edema complicating various diseases including diabetes. The purpose of this study is to evaluate the outcomes of a switch from DEXi to subtenon triamcinolone acetonide (STTA) and back, in eyes with DME. METHODS: Retrospective study. DME eyes that had been treated with DEXi and switched to STTA between October 2018 and February 2019 (stock shortage of DEXi) were included. The functional and anatomical outcomes of the switch and switch-back were studied. RESULTS: 26 eyes of 17 patients (mean age 67.1 ± 8.2 years) were considered. The mean baseline visual acuity (VA) was 0.35 ± 0.17 decimals remaining stable after DEXi, STTA and switch-back to DEXi. The mean central macular thickness (CMT) was 492.7 ± 32.8 µm initially, decreasing to 294.3 ± 133.4 µm after DEXi, 369.9 ± 182.3 µm after STTA and 297.6 ± 72.0 µm after switching back to DEXi (all p < 0.05 versus baseline). Compared to baseline, the CMT reduction was numerically better after DEXi and switching back to DEXi than after STTA (mean reduction: -200.4 µm, -167.7 µm, and -95.08 µm respectively, p = 0.13). Intraocular pressure was comparable after DEXi and STTA. CONCLUSION: DEXi is the steroid of choice in DME. However, STTA can be a cost-effective alternative when DEXi is unavailable or contraindicated. This study suggests that STTA may be used in the context of a step therapy in DME.

Severe macular complications in glaucoma: high-resolution multimodal imaging characteristics and review of the literature.

PURPOSE: To describe imaging characteristics of severe macular complications occurring in glaucoma and discuss available treatments. METHODS: Retrospective case series of glaucomatous patients with macular retinoschisis (MR) and/or serous retinal detachment (SRD). Patients underwent a complete ophthalmological examination and multimodal imaging including retinography, SD-OCT, fluorescein and indocyanine green angiography (FA & ICGA) and adaptive optics (AO). RESULTS: Ten eyes (8 patients) were included. Initial BCVA was 1.04 ± 1.12 logMAR and IOP was 24.0 ± 9.3mmHg. All eyes presented with MR while SRD was present in 5 eyes (5 patients), with a central macular thickness of 573 ± 152 µm. FA and ICGA allowed to exclude leakage in all cases. A focal lamina cribrosa defect (LCD) was found in four eyes (4 patients) using OCT, with AO providing en-face visualization of the defect in one eye. Outer retinal hole was present in 3 eyes (3 patients). No visual improvement or resolution of the macular retinoschisis was observed in eyes with medical or surgical IOP control (N = 9). Vitrectomy with internal membrane limiting peeling and gas tamponade was performed in one eye with good visual results. CONCLUSIONS: Multimodal high-resolution imaging is essential to diagnose severe macular complications associated with advanced glaucoma.

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.

RAPID MACULAR CAPILLARY LOSS IN PATIENTS WITH UNCONTROLLED TYPE 1 DIABETES.

PURPOSE: To analyze the evolution of macular vessel density (VD) over 1 year, during early worsening of diabetic retinopathy, in patients with uncontrolled Type 1 diabetes (T1D). METHODS: Retrospective study of 12 eyes of 9 patients with T1D with early worsening of diabetic retinopathy imaged with optical coherence tomography angiography. The following data were collected at the time of pan retinal photocoagulation initiation and after 6 and 12 months: vessel density within three retinal plexuses-superficial vascular plexus, intermediate capillary plexus, and deep capillary plexus; foveal avascular zone area, acircularity index, and flow density (FD)-300; central macular thickness; and HbA1c levels. RESULTS: A history of rapid reduction in blood glucose was found in seven of nine cases. Vessel density was significantly decreased at 12 months in all plexuses: from 44.68 ± 4.75 to 40.23 ± 7.13 in the superficial vascular plexus (P = 0.008), from 42.72 ± 4.86 to 37.12 ± 8.64 in the intermediate capillary plexus (P = 0.03), and from 22.68 ± 3.93 to 19.66 ± 4.92 in the deep capillary plexus (P = 0.004). Intermediate capillary plexus and deep capillary plexus changes were strongly correlated (r = 0.86, P < 0.001) and were significant as early as 6 months. The mean foveal avascular zone area increased (P = 0.05) and the FD-300 decreased (P = 0.03). No significant change in acircularity index, central macular thickness, and visual acuity were observed over time. CONCLUSION: Early worsening of diabetic retinopathy induces a rapid macular capillary dropout mainly affecting the intermediate capillary plexus and deep capillary plexus.

Evidence of the involvement of dystrophin Dp71 in corneal angiogenesis.

Purpose: The aim of this study was to define the role of dystrophin Dp71 in corneal angiogenesis. Methods: Inflammation-induced corneal neovascularization experiments were performed in Dp71-null mice and C57BL/6J wild-type mice. Results: The corneal neovascular area covered by neovascularization was larger in the injured corneas of the Dp71-null mice compared to the corneas of the wild-type mice: 40.72% versus 26.33%, respectively (p<0.005). Moreover, increased angiogenesis was associated with a high expression of vascular endothelial growth factor (VEGF). Similarly, aortic ring assays showed a significant enhancement of the neovascular area. Conclusions: These results suggest that dystrophin Dp71 could play an important role as a negative regulator of corneal angiogenesis.

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.

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.

Increased corneal sub-basal nerve density in patients with Sjögren syndrome treated with topical cyclosporine A.

BACKGROUND: To evaluate quantitative and qualitative changes in sub-basal corneal nerves (SBN) via in vivo confocal microscopy in patients with Sjögren syndrome dry eye (SSDE) treated with topical cyclosporine A (CsA). DESIGN: Prospective, observational, non-randomized study. PARTICIPANTS: Thirty eyes of 30 patients with SSDE refractory to conventional treatment treated with CsA 0.05% twice daily for 6 months. Fifteen eyes of 15 healthy, age and gender matched, volunteers constituted the control group at baseline. METHODS: A clinical evaluation of dry eye, corneal sensation using Cochet-Bonnet esthesiometry and in vivo confocal microscopy analysis of the central cornea were performed prospectively at baseline for all patients, and after 6 months of treatment with CsA. MAIN OUTCOME MEASURES: Density, number, reflectivity and tortuosity of SBN, dendritic cell (DC) density, esthesiometry, and dry eye signs and symptoms. RESULTS: Topical CsA 0.05% improved clinical signs and symptoms, and increased corneal sensitivity. Following treatment, SBN density was significantly increased (P < 0.0001) associated with a decreased in DC density (P < 0.0001). The increase in SBN density after treatment was positively correlated with baseline SBN density (R2  = 0.33; P = 0.0008) and negatively correlated with baseline Ocular Surface Disease Index (R2  = 0.28; P = 0.002), Oxford score (R2  = 0.31; P = 0.002), and DC density (R2  = 0.37; P = 0.0003). CONCLUSIONS: Topical CsA led to an increase in corneal SBN density, improving clinical signs and symptoms of SSDE. Our results also suggest an improved response to treatment in patients with less initial nerve damage.

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.

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.

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.

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.

Eye disorders other than diabetic retinopathy in patients with diabetes.

AIM: While diabetic retinopathy is the most specific complication of chronic hyperglycaemia, numerous other ocular conditions also can involve the eyes of people with diabetes. Cataract, glaucoma, age-related macular degeneration, retinal vascular occlusion, and acute ischaemic optic neuropathy combine to impair vision in people with diabetes, especially when they are old. This report provides a critical analysis and an overview of the current knowledge of the main ocular disorders (excluding diabetic retinopathy) and their association in patients with diabetes. METHODS: A literature search strategy was conducted for all English-language literature with a systematic review of key references until 2021. RESULTS: Patients with diabetes have a high-to-moderate increased risk for most of the usual ocular disorders we reviewed with the exception of age-related macular degeneration. Exposure to chronic hyperglycaemia promotes the development of many eye disorders while acute glucose changes are involved in refractive disorders, diabetic papillopathy and acute cataract. CONCLUSION: Diabetes, beyond diabetic retinopathy, increases the risk of numerous eye disorders leading to low vision with implications for daily diabetes management. Even in the absence of clearly demonstrated benefit from glucose control in all eye conditions, achieving good glycaemic control and adherence to diabetes treatment will likely help avoid an additional risk of visual impairment in people with diabetes. In perspective, interesting findings suggesting a preventive effect of metformin use on age-related macular degeneration occurrence justify further studies.

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

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

Agreement of time-domain and spectral-domain optical coherence tomography with fluorescein leakage from choroidal neovascularization.

PURPOSE: To compare fluorescein leakage from choroidal neovascularization (CNV) with signs of intraretinal or subretinal fluid on time-domain optical coherence tomography (TD-OCT) and spectral-domain optical coherence tomography (SD-OCT) in patients receiving anti-vascular endothelial growth factor (anti-VEGF) therapy for CNV caused by age-related macular degeneration (AMD). DESIGN: Retrospective, consecutive case series. PARTICIPANTS: Fifty-nine eyes of 56 patients with neovascular AMD receiving anti-VEGF therapy. METHODS: All patients were imaged with fluorescein angiography (FA), TD-OCT (Stratus, Carl Zeiss Meditec, Inc., Dublin, CA), and SD-OCT (Cirrus, Carl Zeiss Meditec, Inc). All images were analyzed by an experienced reading center grader masked to all clinical data. Fluorescein leakage from CNV and OCT abnormalities (presence of interstitial fluid, retinal cystoid abnormalities, and subretinal fluid) were documented for each visit. MAIN OUTCOME MEASURES: Agreement of OCT findings with presence or absence of fluorescein leakage from CNV. RESULTS: For TD-OCT, the sensitivity, specificity, positive predictive value, and negative predicative value (and 95% confidence intervals) for OCT abnormalities were 59% (46-72), 63% (50-75%), 61% (49-73), and 61% (48-74), respectively. For SD-OCT, the sensitivity, specificity, positive predictive value, and negative predictive value (and 95% confidence intervals) for OCT abnormalities were 90% (82-98), 47% (34-60), 62% (49-75), and 82% (72-92), respectively. CONCLUSIONS: Spectral-domain optical coherence tomography seems more likely than TD-OCT to detect abnormalities when fluorescein leakage from CNV is detected after anti-VEGF therapy. However, SD-OCT also seems to detect abnormalities frequently in the absence of fluorescein leakage from CNV. Whether treatment decisions based on any of these modalities result in visual acuity outcomes that are similar or superior to monthly treatments without such evaluations is unknown, but this study provides information that may assist in the design of studies to evaluate the role of OCT and FA in the management of CNV. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

High Molecular Weight Hyaluronan Promotes Corneal Nerve Growth in Severe Dry Eyes.

The purpose of this study was to investigate the effect of high molecular weight hyaluronan (HMWHA) eye drops on subbasal corneal nerves in patients suffering from severe dry eye disease (DED) and to evaluate the damage of subbasal corneal nerves associated with severe DED. Designed as an international, multicenter study, 16 patients with symptoms of at least an Ocular Surface Disease Index (OSDI) score of 33, and corneal fluorescein staining (CFS) of at least Oxford grade 3, were included and randomized into two study arms. The control group continued to use their individual optimum artificial tears over the study period of eight weeks; in the verum group, the artificial tears were substituted by eye drops containing 0.15% HMWHA. At the baseline visit, and after eight weeks, the subbasal nerve plexus of 16 patients were assessed by confocal laser scanning microscopy (CSLM). The images were submitted to a masked reading center for evaluation. Results showed a significant increase of total nerve fiber lengths (CNFL) in the HMWHA group (p = 0.030) when compared to the control group, where the total subbasal CNFL did not significantly change from baseline to week 8. We concluded that in severe DED patients, HMWHA from topically applied eye drops could cross the epithelial barrier and reach the subbasal nerve plexus, where it exercised a trophic effect.

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).