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.

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.

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.

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.

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.

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.

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.

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).

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.

Reduced vessel density in the superficial and deep plexuses in diabetic retinopathy is associated with structural changes in corresponding retinal layers.

PURPOSE: To explore the relationships between vessel density (VD) in the retinal vascular plexuses with the thickness and structural changes of their corresponding retinal layers in patients with diabetic retinopathy (DR). METHODS: Retrospective analysis of 17 eyes of 17 Type 1 diabetes (T1D) patients with severe non-proliferative or proliferative DR and no current or past macular edema. Seventeen age- and sex-matched healthy subjects were included as controls. Using optical coherence tomography (OCT) and OCT-angiography (OCTA), VD was measured in the superficial vascular plexus (SVP) and deep vascular complex (DVC) that includes the intermediate (ICP) and deep capillary plexuses (DCP), and compared to the retinal thickness (RT) of the inner (from the inner limiting membrane to the inner plexiform layer) and intermediate (inner nuclear and outer plexiform layer) retinal layers. The correlation between the inner and intermediate RT and the VD of the corresponding vascular networks (SVP and DVC, respectively) was assessed. All OCT and OCTA examinations were performed using the RTVue XR Avanti (Optovue, Fremont, CA). RESULTS: The inner RT and VD in all plexuses were significantly reduced in T1D patients compared to healthy subjects. The capillary drop-out patterns were polygonal and well-defined in the SVP while the ICP and DCP showed a more diffuse capillary rarefaction and a VD that varied in the same proportion. The inner RT significantly correlated with VD in the SVP (r = 0.71 in healthy subjects and r = 0.62 in T1D patients, p <0.01). The intermediate RT did not significantly correlate with VD in the DVC. CONCLUSIONS: In T1D subjects, OCTA allowed observing different capillary drop-out patterns in the SVP and in the ICP-DCP, with different structural changes in the corresponding retinal layers, suggesting that they should be considered as distinct anatomical and functional entities.

Efficacy of a Topical Heparan Sulfate Mimetic Polymer on Ocular Surface Discomfort in Patients with Cogan's Epithelial Basement Membrane Dystrophy.

Purpose: Treatment of persistent ocular discomfort in patients with Cogan's epithelial basement membrane dystrophy (EBMD) is a challenge for ophthalmologists. This study aimed to determine the efficacy of a topical heparan sulfate mimetic polymer (HSMP) in reducing ocular discomfort in EBMD patients. Methods: This retrospective, noninterventional study included 22 consecutive patients in 3 tertiary ophthalmological units with spontaneous, recurrent, acute ocular pain, resistant to various topical lubricants. After EBMD diagnosis, HSMP treatment was initiated while lubricating eye drops were continued. The main study outcome was the change in ocular discomfort assessed using the ocular surface disease index (OSDI) from initiation of treatment to last follow-up visit. Results: The mean OSDI decreased from 46.7 ± 22.3 to 31.6 ± 17.4 (P < 0.001) at first visit and 32.5 ± 17.9 (P < 0.01) at last visit. The rate of patients with severe ocular surface disease (OSDI >33) decreased from 68.2% to 36.4% at first visit and 42.9% at last visit. After a median follow-up of 8.5 months, 7 (31.8%) patients discontinued the HSMP treatment due to a marked improvement in ocular surface comfort and no recurrence of ocular pain, 5 (22.7%) due to lack of efficacy, and 1 (4.5%) due to an ocular adverse event (not treatment related). Eight patients continued treatment after the last visit and 1 patient was lost to follow-up. Globally, HSMP prevented acute painful episodes in 11 (61.1%) of 18 patients followed for ∼4 months. Conclusions: Topical HSMP may be an option for alleviating ocular discomfort in patients with EBMD resistant to standard symptomatic treatments.

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.].