Implantable vision-enhancing devices and postoperative rehabilitation in advanced age-related macular degeneration.

Age-related macular degeneration (AMD) results in progressive vision loss that significantly impacts patients' quality of life and ability to perform routine daily activities. Although pharmaceutical treatments for AMD are available and in clinical development, patients with late-stage AMD are relatively underserved. Specialized rehabilitation programs and external low-vision aids are available to support visual performance for those with advanced AMD; but intraocular vision-improving devices, including implantable miniature telescope (IMT) and intraocular lens (IOL) implants, offer advantages regarding head motion, vestibular ocular reflex development, and depth perception. IMT and IOL technologies are rapidly evolving, and many patients who could benefit from them remain unidentified. This review of recent literature summarizes available information on implantable devices for improving vision in patients with advanced AMD. Furthermore, it discusses recent attempts of developing the quality of life tests including activities of daily life and objective assessments. This may offer the ophthalmologist but also the patient a better possibility to detect changes or improvements before and after surgery. It is evident that surgery with new implants/devices is no longer the challenge, but rather the more complex management of patients before and after surgery as well as the correct selection of cases.

The Value of Optical Coherence Tomography Angiography (OCT-A) in Neurological Diseases.

Optical coherence tomography angiography (OCT-A) was commercially introduced in 2014. OCT-A allows a fast, non-invasive, three-dimensional analysis of the retinal vasculature from the vitreoretinal interface to the choriocapillaris. The results can be evaluated separately in automated or custom-defined retinal layers. Since its introduction, OCT-A has also been used in patients with neurological diseases in order to find and characterize retinal biomarkers. Many neurological diseases have retinal manifestations, often preceding the key symptoms of the neurological disease. Anatomically and developmentally, the retina is a part of the brain. In contrast to the brain, the retina is easily accessible for imaging methods; moreover, retinal imaging is more cost-effective than brain imaging. In this review, the current knowledge about OCT-A findings and possible OCT-A biomarkers in neurological diseases is summarized and discussed regarding the value of OCT-A as a diagnostic tool in neurological diseases.

Assessment of Reinjection Numbers and Intervals for Diabetic Macular Edema Patients Who Received Dexamethasone Intravitreal Implants in Germany and Switzerland.

PURPOSE: The purpose was to assess the number and intervals of dexamethasone intravitreal implant (DEX) reinjections in a real-world setting for the treatment of diabetic macular edema (DME) and to determine the relationship with effectiveness and safety. PATIENTS AND METHODS: Data were abstracted from medical records of DME patients in Germany and Switzerland for this retrospective, multicenter, drug utilization study. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) changes 7-12 weeks post-injection(s) measured effectiveness. Adverse events (AEs) of special interest were reported. RESULTS: A total of 141 patients, 108 from Germany and 33 from Switzerland, were assessed. Mean (SD) reinjection interval was 5.7 (4.2) months. Mean baseline BCVA was 61.6 letters, and mean baseline CRT was 413.3 µm. The mean BCVA and CRT changes at 7-12 weeks after baseline, reinjection 1, 2, and 3 were +3.4, +3.7, +3.2, and -1.4 letters and -88.3, -81.6, -102.4, and -124.1 µm, respectively. The Spearman correlation between change in BCVA and CRT and DEX reinjection interval was r=0.03 (P=0.66) and r=0.07 (P=0.38), respectively. Only 18% of patients experienced at least 1 AE. CONCLUSION: There was no statistically significant correlation between drug effectiveness and reinjection intervals in either country. Although these results are preliminary, they indicate that DEX improves BCVA and CRT in real-world clinical practice.

Prevention of the Onset of Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) represents the leading cause of irreversible blindness in elderly people, mostly after the age of 65. The progressive deterioration of visual function in patients affected by AMD has a significant impact on quality of life and has also high social costs. The current therapeutic options are only partially able to slow down the natural course of the disease, without being capable of stopping its progression. Therefore, better understanding of the possibilities to prevent the onset of the disease is needed. In this regard, a central role is played by the identification of risk factors, which might participate to the development of the disease. Among these, the most researched are dietary risk factors, lifestyle, and light exposure. Many studies showed that a higher dietary intake of nutrients, such as lutein, zeaxanthin, beta carotene, omega-3 fatty acids and zinc, reduced the risk of early AMD. Regarding lifestyle habits, the association between smoking and AMD is currently accepted. Finally, retinal damage caused by ultraviolet rays and blue light is also worthy of attention. The scope of this review is to summarize the present knowledge focusing on the measures to adopt in order to prevent the onset of AMD.

The impact of vitrectomy on outcomes achieved with 0.19 mg fluocinolone acetonide implant in patients with diabetic macular edema.

BACKGROUND: There is a lack of consensus on the use of intravitreal corticosteroid therapies in patients with diabetic macular edema (DME) and prior vitrectomized eyes in clinical practice. METHODS: Retro-IDEAL was a 3-year retrospective, multicenter study in patients with chronic DME (i.e. DME that persists or recurs despite treatment) treated with ILUVIEN® (0.2 µg daily fluocinolone acetonide intravitreal implant), who had suboptimal outcomes with first-line vascular endothelial growth-factor inhibitors and other DME therapies. RESULTS: A total of 81 eyes (63 patients) were included of which 39 eyes had undergone prior vitrectomy (PV group) while 42 eyes had not undergone prior vitrectomy (NPV). Baseline characteristics were balanced; however, more patients had proliferative diabetic retinopathy in the PV group vs. the NPV group (21.62% vs 9.38%, respectively). Over 36 months, mean visual acuity (VA) increased in both groups with a tendency for more ETDRS letters being gained in the NPV group (+5.33) vs. the PV group (+2.42). By month 36, central retinal thickness was reduced to ⩽300 µm in two-thirds of the eyes in both groups and the mean change from baseline in intraocular pressure was similar in both groups (+0.50 mmHg -0.75 mmHg; NPV and PV group). CONCLUSIONS: These long-term data suggest that the 0.2 µg/day FAc implant is effective in both vitrectomized and non-vitrectomized patients, with a manageable safety profile, and improved VA and reduced supplemental therapies for patients with a suboptimal response to first-line DME therapies. Clinicians may consider utilizing the FAc implant earlier in the DME disease process.

[Clinical Decision Making for Treatment of Diabetic Macular Oedema with DEX Implant: a Consensus Paper]. / Klinische Entscheidungsfindung bei der Behandlung des diabetischen Makulaödems mit DEX-Implantat: ein Konsenspapier.

BACKGROUND: Currently two intravitreally applied corticosteroids (dexamethasone and fluocinolone) are licensed in Germany for treatment of diabetic macular oedema (DME). The use of DEX implant for DME in daily clinical practice has not been defined in detail. Following a Delphi panel survey, a group of retina experts set out to come up with a consensus for use of the DEX implant in DME. MATERIAL AND METHODS: International and national treatment recommendations were identified from the literature. A steering group generated a catalogue of 72 statements on the aetiology and pathogenesis of DME, therapy with DEX implant, use of DEX implant in patients previously treated with VEGF-inhibitors, use of DEX implant in combination therapy, safety of DME therapies as well as patients' burden of treatment. Twenty-two ophthalmologists from private practice and 6 hospital ophthalmologists participated in the Delphi panel via Survey Monkey. Consensus was reached if at least 75% of participants agreed or disagreed with a statement. Statements for which consensus was not reached were discussed once more during the expert consensus meeting and a vote was taken. Based on these results a treatment algorithm for foveal DME was proposed. RESULTS: If a patient does not show sufficient response after 3 - 6 months of anti-VEGF treatment (visual acuity gain of < 5 ETDRS letters or reduction of central retinal thickness ≤ 20%), a switch to DEX implant should take place. DEX implant is also suitable in eyes with longer presentation of DME, showing e.g. massive lipid exudates. DEX implant is suitable as first-line therapy especially in pseudophakic patients, patients unwilling or able to comply with tight anti-VEGF injection intervals or patients with known vascular diseases. With fixed control visits every 4 - 8 weeks, use of DEX implant is flexible and individual. Decision parameters for repeated use should be visual acuity, retinal thickness and intraocular pressure. Treatment of both eyes on the same day should not take place. CONCLUSION: The algorithm presented reflects survey as well as expert discussion results and may differ from recommendations issued by the German professional society. The consensus recommendations for the treatment of DME generated during the survey and meeting of retina experts are intended to guide use of DEX implant in daily practice.

PHASE 2 STUDY OF THE SAFETY AND EFFICACY OF BRIMONIDINE DRUG DELIVERY SYSTEM (BRIMO DDS) GENERATION 1 IN PATIENTS WITH GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate the safety and efficacy of Brimonidine Drug Delivery System (Brimo DDS), a biodegradable intravitreal implant, in the treatment of geographic atrophy (GA) secondary to age-related macular degeneration. METHODS: Phase 2, randomized, multicenter, double-masked, 24-month study. Study eyes were treated (Day 1; Month 6 retreatment) with Brimo DDS 132 µg (n = 49), Brimo DDS 264 µg (n = 41), or sham procedure (n = 23). The primary timepoint for efficacy analysis was Month 12. RESULTS: Mean GA area growth at Month 12 was 1.78 mm2, 1.59 mm2, and 2.19 mm2 in the Brimo DDS 132 µg, 264 µg, and sham groups, respectively. Geographic atrophy area growth was consistently smaller with Brimo DDS 132 and 264 µg than sham; between-group differences were significant (P ≤ 0.032) at Month 3. In patients with baseline lesion area ≥6 mm2 (two-thirds of patients), GA lesion area and effective radius growth was reduced with Brimo DDS 132 and 264 µg at Month 12 (P ≤ 0.050 vs. sham). Treatment-related adverse events were usually injection procedure-related. CONCLUSION: Brimo DDS demonstrated a favorable safety profile and reduced GA lesion area growth at Month 3. Lesion growth at Month 12 was reduced in patients with baseline GA lesion area ≥6 mm2. The results support Phase 3 development.

Current concepts of pharmacotherapy of diabetic macular edema.

Introduction: Diabetic macular edema (DME) is a sight threatening disease and a major cause for blindness for people in working age. The pathogenesis is multifactorial and complex. The pharmacotherapy of DME addresses both the inhibition of vascular endothelial growth factor (VEGF) by the intravitreal injection of VEGF inhibitors and inflammatory processes by the intravitreal application of steroids. Several trials have been published reporting on the efficacy and safety of these treatments.Areas covered: This review discusses original research articles including basic science and clinical studies as well as review articles focusing on the role of inflammation and VEGF expression in DME. It discusses newly published clinical trials on intravitreal pharmacotherapy for DME. The literature was searched using Medline/PubMed and was selected given its relevance for the topic to be discussed.Expert opinion: Our knowledge regarding the pathophysiology of diabetic macular edema has significantly increased. Some of these insights have been successfully transferred into current treatment strategies already including VEGF suppression or anti-inflammatory treatments using steroids. The identification of additional pathophysiological aspects and their relevance as potential treatment targets will be a future challenge in the treatment of DME. A better knowledge on the complex pathophysiology will also help to establish combination strategies.

ADVERSE EVENTS OF THE ARGUS II RETINAL PROSTHESIS: Incidence, Causes, and Best Practices for Managing and Preventing Conjunctival Erosion.

PURPOSE: To analyze and provide an overview of the incidence, management, and prevention of conjunctival erosion in Argus II clinical trial subjects and postapproval patients. METHODS: This retrospective analysis followed the results of 274 patients treated with the Argus II Retinal Prosthesis System between June 2007 and November 2017, including 30 subjects from the US and European clinical trials, and 244 patients in the postapproval phase. Results were gathered for incidence of a serious adverse event, incidence of conjunctival erosion, occurrence sites, rates of erosion, and erosion timing. RESULTS: Overall, 60% of subjects in the clinical trial subjects versus 83% of patients in the postapproval phase did not experience device- or surgery-related serious adverse events. In the postapproval phase, conjunctival erosion had an incidence rate of 6.2% over 5 years and 11 months. In 55% of conjunctival erosion cases, erosion occurred in the inferotemporal quadrant, 25% in the superotemporal quadrant, and 20% in both. Sixty percent of the erosion events occurred in the first 15 months after implantation, and 85% within the first 2.5 years. CONCLUSION: Reducing occurrence of conjunctival erosion in patients with the Argus II Retinal Prosthesis requires identification and minimization of risk factors before and during implantation. Implementing inverted sutures at the implant tabs, use of graft material at these locations as well as Mersilene rather than nylon sutures, and accurate Tenon's and conjunctiva closure are recommended for consideration in all patients.

Relationship between duration and extent of oedema and visual acuity outcome with ranibizumab in diabetic macular oedema: A post hoc analysis of Protocol I data.

BACKGROUND/OBJECTIVES: This post hoc analysis explores the relationship between residual oedema exposure after ranibizumab treatment initiation and long-term visual acuity outcome in eyes with centre-involved diabetic macular oedema (DMO). SUBJECTS/METHODS: Eyes randomised to the ranibizumab + prompt or deferred laser treatment arms in the Protocol I trial and with observed central retinal thickness (CRT) readings at baseline and ≥1 follow-up visits (n = 367) were stratified by 1) oedema duration (number of study visits with CRT ≥ 250 µm during the first 52 weeks of ranibizumab treatment); and 2) oedema extent (amount of excess CRT [≥ 250 µm] at each study visit, averaged over the first 52 weeks). Associations between measures of residual oedema and best-corrected visual acuity (BCVA) were assessed in multiple regression analyses. RESULTS: Oedema duration and oedema extent during the first 52 weeks of ranibizumab treatment showed significant negative associations with BCVA improvement at weeks 52, 104 and 156. Eyes with the most persistent oedema gained (mean) 4.4 (95% CI 0.1─8.7) fewer Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 156 than eyes with the least persistent oedema (P = 0.044). Eyes with the greatest amount of oedema gained (mean) 9.3 (95% CI 4.0─14.5) fewer ETDRS letters at week 156 than eyes with the least amount of oedema (P < 0.001). CONCLUSIONS: Macular oedema exposure over the first 52 weeks of ranibizumab treatment is a negative prognostic factor for long-term visual acuity improvement in centre-involved DMO.

Three-year results from the Retro-IDEAL study: Real-world data from diabetic macular edema (DME) patients treated with ILUVIEN® (0.19 mg fluocinolone acetonide implant).

INTRODUCTION: The Retro-IDEAL (ILUVIEN Implant for chronic DiabEtic MAcuLar edema) study is a retrospective study designed to assess real-world outcomes achieved with the ILUVIEN® (0.19 mg fluocinolone acetonide (FAc)) in patients with chronic diabetic macular edema (DME) in clinical practices in Germany. METHODS: This study was conducted across 16 sites in Germany and involved 81 eyes (63 patients) with persistent or recurrent DME and a prior suboptimal response to a first-line intravitreal therapy (primarily anti-VEGF intravitreal therapies). RESULTS: Patients were followed-up for 30.8 ± 11.3 months (mean ± standard deviation) and had a mean age of 68.0 ± 10.4 years. Best-recorded visual acuity (BRVA) improved by +5.5 letters at month 9 (P ⩽ 0.005, n=56; from a baseline of 49 letters) and this was maintained through to month 30 (P ⩽ 0.05, n = 42). There was a concurrent improvement in central macular thickness with a reduction from 502 µm at baseline to 338 µm at year 1 (P ⩽ 0.0001, n = 43). This effect was sustained to year 3 (i.e. 318 µm; P ⩽ 0.0001, n = 29). Mean intraocular pressure (IOP) remained constant between baseline and year 3 with a peak change of 1.9 mm Hg occurring at year 1. Elevated IOP was observed in a similar percentage of patients prior to (22.2% of cases) and following (27.2%) treatment with the FAc implant. In the majority of cases, these elevations were managed effectively with IOP medications. CONCLUSIONS: Despite substantial amounts of prior intravitreal treatments - primarily with anti-vascular endothelial growth factor (VEGF) drugs - this real-world study showed that sustained structural and functional improvements can last for up to 3 years with a single FAc implant.

An optical coherence tomography-based grading of diabetic maculopathy proposed by an international expert panel: The European School for Advanced Studies in Ophthalmology classification.

AIMS: To present an authoritative, universal, easy-to-use morphologic classification of diabetic maculopathy based on spectral domain optical coherence tomography. METHODS: The first draft of the project was developed based on previously published classifications and a literature search regarding the spectral domain optical coherence tomography quantitative and qualitative features of diabetic maculopathy. This draft was sent to an international panel of retina experts for a first revision. The panel met at the European School for Advanced Studies in Ophthalmology headquarters in Lugano, Switzerland, and elaborated the final document. RESULTS: Seven tomographic qualitative and quantitative features are taken into account and scored according to a grading protocol termed TCED-HFV, which includes foveal thickness (T), corresponding to either central subfoveal thickness or macular volume, intraretinal cysts (C), the ellipsoid zone (EZ) and/or external limiting membrane (ELM) status (E), presence of disorganization of the inner retinal layers (D), number of hyperreflective foci (H), subfoveal fluid (F), and vitreoretinal relationship (V). Four different stages of the disease, that is, early diabetic maculopathy, advanced diabetic maculopathy, severe diabetic maculopathy, and atrophic maculopathy, are based on the first four variables, namely the T, C, E, and D. The different stages reflect progressive severity of the disease. CONCLUSION: A novel grading system of diabetic maculopathy is hereby proposed. The classification is aimed at providing a simple, direct, objective tool to classify diabetic maculopathy (irrespective to the treatment status) even for non-retinal experts and can be used for therapeutic and prognostic purposes, as well as for correct evaluation and reproducibility of clinical investigations.

Isolated Intraocular Rosai-Dorfman Disease.

BACKGROUND/AIMS: To report a case of Rosai-Dorfman disease (RDD) presenting as a solitary, choroidal mass, initially suspicious for uveal melanoma, in a 72-year-old woman. METHODS: Retrospective case report of a single patient. RESULTS: A 72-year-old woman presented with sudden vision loss in the right eye. A month prior, visual acuity was 20/40, but she was noted to have a choroidal mass confirmed with B-scan ultrasonography. Patient's vision deteriorated significantly a month later and a shallow retinal detachment was newly noted. Magnetic resonance imaging was obtained, demonstrating a hyperintense intraocular tumor on TI imaging. Patient underwent enucleation of the right eye for suspicion of a uveal melanoma. Pathology revealed a mixed cellular infiltrate with histiocytes, some exhibiting emperipolesis. Macrophage immunohistochemical stains were positive, while melanocytic markers were negative. A diagnosis of RDD was made. Subsequently, the patient had a negative workup for systemic involvement. A final diagnosis of intraocular RDD without extraocular and systemic involvement was determined. CONCLUSION: We describe a rare presentation of RDD as a solitary choroidal mass in an elderly patient with overlapping features of uveal melanoma. Definitive diagnosis could only be made on histology. RDD should be considered in the differential diagnosis of a choroidal lesion in the elderly.

Natural history of diabetic macular edema and factors predicting outcomes in sham-treated patients (MEAD study).

PURPOSE: To describe the natural history of diabetic macular edema (DME) with respect to best-corrected visual acuity (BCVA) and central retinal thickness (CRT) outcomes and to identify baseline patient characteristics and systemic factors associated with improvement or worsening of outcomes in sham-treated patients. METHODS: The study population was sham-treated patients (n = 350) in the 3-year MEAD registration study of dexamethasone intravitreal implant for treatment of DME. Patients had center-involved DME and received sham intravitreal injections in the study eye at ≥ 6-month intervals. Potential prognostic factors for outcomes were evaluated using multiple linear regression analysis. RESULTS: Visual and anatomic outcomes were poorer in patients who left the study early (n = 198) than in study completers (n = 152). Mean change in BCVA from baseline at the last visit with available data was + 0.9 letters; 37.5% of patients had no change in BCVA, 23.2% had gained > 10 letters, and 16.0% had lost > 10 letters. Older age and baseline diabetic retinopathy score > 6 were associated with worse BCVA outcomes; thicker baseline CRT and larger number of hypertension medications used were associated with larger reductions in CRT during the study. CONCLUSIONS: BCVA and CRT outcomes were variable in this population of DME patients with generally good glycemic control. In DME patients without active treatment, older age and baseline diabetic retinopathy score > 6 were associated with less improvement in BCVA; thicker baseline CRT and a larger number of antihypertensive medications used predicted better improvement in CRT. TRIAL REGISTRATION: The MEAD study trials are registered at ClinicalTrials.gov with the identifiers NCT00168337 and NCT00168389.

ASSOCIATION BETWEEN EARLY ANATOMIC RESPONSE TO ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY AND LONG-TERM OUTCOME IN DIABETIC MACULAR EDEMA: An Independent Analysis of Protocol i Study Data.

PURPOSE: This post hoc analysis explores the relationship between early retinal anatomical response and long-term anatomical and visual outcomes with ranibizumab in center-involved diabetic macular edema. METHODS: Eyes randomized to the ranibizumab plus prompt laser and ranibizumab plus deferred laser treatment arms in the Protocol I study were categorized according to their proportional reduction (<20 vs. ≥20%) in central retinal thickness (CRT) after 12 weeks. Adjusted and unadjusted analyses assessed the association between early (Week 12) anatomical response and long-term (Weeks 52 and 156) anatomical and best-corrected visual acuity outcomes. RESULTS: Of 335 study eyes, 118 showed limited (<20%) and 217 showed strong (≥20%) CRT reduction at Week 12. In unadjusted and adjusted analyses, limited early CRT response was negatively and significantly associated with strong CRT response at Weeks 52 and 156. Sensitivity analyses indicated that this association was robust and unrelated to any "floor effect." In unadjusted analyses, a strong early CRT response was associated with greater long-term improvement in best-corrected visual acuity; after controlling for confounders, the association lost statistical significance. CONCLUSION: Early CRT response to ranibizumab is a significant prognostic indicator of medium- to long-term anatomical outcome in center-involved diabetic macular edema.

Retinal Anatomy and Electrode Array Position in Retinitis Pigmentosa Patients After Argus II Implantation: An International Study.

PURPOSE: To assess the retinal anatomy and array position in Argus II retinal prosthesis recipients. DESIGN: Prospective, noncomparative cohort study. METHODS: Setting: International multicenter study. PATIENTS: Argus II recipients enrolled in the Post-Market Surveillance Studies. PROCEDURES: Spectral-domain optical coherence tomography images collected for the Surveillance Studies (NCT01860092 and NCT01490827) were reviewed. Baseline and postoperative macular thickness, electrode-retina distance (gap), optic disc-array overlap, and preretinal membrane presence were recorded at 1, 3, 6, and 12 months. MAIN OUTCOME MEASURES: Axial retinal thickness and axial gap along the array's long axis (a line between the tack and handle); maximal retinal thickness and maximal gap along a B-scan near the tack, midline, and handle. RESULTS: Thirty-three patients from 16 surgical sites in the United States and Germany were included. Mean axial retinal thickness increased from month 1 through month 12 at each location, but reached statistical significance only at the array midline (P = .007). The rate of maximal thickness increase was highest near the array midline (slope = 6.02, P = .004), compared to the tack (slope = 3.60, P < .001) or the handle (slope = 1.93, P = .368). The mean axial and maximal gaps decreased over the study period, and the mean maximal gap size decrease was significant at midline (P = .032). Optic disc-array overlap was seen in the minority of patients. Preretinal membranes were common before and after implantation. CONCLUSIONS: Progressive macular thickening under the array was common and corresponded to decreased electrode-retina gap over time. By month 12, the array was completely apposed to the macula in approximately half of the eyes.