Retinal Prostheses: Engineering and Clinical Perspectives for Vision Restoration.

A retinal prosthesis, also known as a bionic eye, is a device that can be implanted to partially restore vision in patients with retinal diseases that have resulted in the loss of photoreceptors (e.g., age-related macular degeneration and retinitis pigmentosa). Recently, there have been major breakthroughs in retinal prosthesis technology, with the creation of numerous types of implants, including epiretinal, subretinal, and suprachoroidal sensors. These devices can stimulate the remaining cells in the retina with electric signals to create a visual sensation. A literature review of the pre-clinical and clinical studies published between 2017 and 2023 is conducted. This narrative review delves into the retinal anatomy, physiology, pathology, and principles underlying electronic retinal prostheses. Engineering aspects are explored, including electrode-retina alignment, electrode size and material, charge density, resolution limits, spatial selectivity, and bidirectional closed-loop systems. This article also discusses clinical aspects, focusing on safety, adverse events, visual function, outcomes, and the importance of rehabilitation programs. Moreover, there is ongoing debate over whether implantable retinal devices still offer a promising approach for the treatment of retinal diseases, considering the recent emergence of cell-based and gene-based therapies as well as optogenetics. This review compares retinal prostheses with these alternative therapies, providing a balanced perspective on their advantages and limitations. The recent advancements in retinal prosthesis technology are also outlined, emphasizing progress in engineering and the outlook of retinal prostheses. While acknowledging the challenges and complexities of the technology, this article highlights the significant potential of retinal prostheses for vision restoration in individuals with retinal diseases and calls for continued research and development to refine and enhance their performance, ultimately improving patient outcomes and quality of life.

Paracentral acute middle maculopathy in a fasting patient after cataract surgery and its response to hyperbaric oxygen therapy.

INTRODUCTION: Paracentral acute middle maculopathy (PAMM) is a structural optical coherence tomography (OCT) sign secondary to ischemia in the intermediate and deep retinal vascular network, characterized by hyperreflectivity in the inner nuclear layer (INL). AIM: Our objective is to demonstrate PAMM development following uncomplicated cataract surgery, possibly triggered by fasting and dehydration. We also aim to emphasize the potential role of hyperbaric oxygen therapy in treating PAMM. CASE PRESENTATION: A 66-year-old man with a past medical history of Neurofibromatosis type 1 and cardiovascular disease underwent uncomplicated cataract surgery in the left eye. The patient was also fasting due to Ramadan. The patient complained of very low vision during the routine postoperative examination on the third day. His-best-corrected visual acuity (BCVA) was counting fingers at 1 meter. His-anterior and posterior segment examination was unremarkable. In infrared imaging, a large hyporeflective area was observed in the parafoveal region, and structural OCT also showed increased hyperreflectivity in the middle retinal layers corresponding to the junction of INL and outer plexiform layer (OPL) involving the entire INL which suggested PAMM. Following 14 sessions of hyperbaric oxygen therapy, the patient's BCVA increased to 0.9 on the 14th day of diagnosing PAMM. CONCLUSION: To the best of our knowledge, this is the first case representing a patient with  PAMM triggered by fasting and cataract surgery who responded positively to hyperbaric oxygen therapy. However, triggering of PAMM by fasting is entirely unproven and that this observation occurred in a highly complex case with many other possible contributing factors. Also, the triggering of PAMM by some manipulation during surgery is equally unproven.

Hyperbaric Oxygen Therapy Combined with Immunosuppression for Acute Macular Neuroretinopathy in Systemic Lupus Erythematosus.

PURPOSE: To describe the use of hyperbaric oxygen therapy (HBOT) in conjunction with immunosuppression for acute macular neuroretinopathy (AMN) in systemic lupus erythematosus (SLE). METHODS: Two known cases of SLE presented to us with blurred vision and paracentral scotomas due to AMN. Both cases reported worsening of their conditions despite the initiation of high-dose steroid therapy. HBOT was added on as a treatment modality to address vaso-occlusive ischemic injury. RESULTS: Both patients underwent a total of twelve cycles of HBOT. Functional and anatomical improvements were noted immediately after the initiation of therapy and were maintained over more than one year of follow-up. No significant retinal thinning was noted on optical coherence tomography on disease resolution, as has been noted previously. Visual field scotoma showed a complete resolution. CONCLUSION: Our cases suggest that HBOT may have a role in aiding functional and anatomical recovery in AMN associated with SLE.

Retinal Temperature Determination Based on Photopic Porcine Electroretinogram.

OBJECTIVE: Subthreshold retinal laser therapy (SLT) is a treatment modality where the temperature of the retinal pigment epithelium (RPE) is briefly elevated to trigger the therapeutic benefits of sublethal heat shock. However, the temperature elevation induced by a laser exposure varies between patients due to individual differences in RPE pigmentation and choroidal perfusion. This study describes an electroretinography (ERG)-based method for controlling the temperature elevation during SLT. METHODS: The temperature dependence of the photopic ERG response kinetics were investigated both ex vivo with isolated pig retinas and in vivo with anesthetized pigs by altering the temperature of the subject and recording ERG in different temperatures. A model was created for ERG-based temperature estimation and the feasibility of the model for controlling SLT was assessed through computational simulations. RESULTS: The kinetics of the photopic in vivo flash ERG signaling accelerated between 3.6 and 4.7%/°C, depending on the strength of the stimulus. The temperature dependence was 5.0%/°C in the entire investigated range of 33 to 44°C in ex vivo ERG. The simulations showed that the method is suitable for determining the steady-state temperature elevation in SLT treatments with a sufficiently long laser exposure and large spot size, e.g., during > 30 s laser exposures with > 3 mm stimulus spot diameter. CONCLUSIONS: The described ERG-based temperature estimation model could be used to control SLT treatments such as transpupillary thermotherapy. SIGNIFICANCE: The introduced ERG-based method for controlling SLT could improve the repeatability, safety, and efficacy of the treatment of various retinal disorders.

Lentiviral vector-mediated expression of C3 transferase attenuates retinal ischemia and reperfusion injury in rats.

AIMS: Our previous study showed that intravitreal delivery of self-complementary AAV2 (scAAV2)-mediated exoenzyme C3 transferase (C3) can attenuate retinal ischemia/reperfusion (I/R) injury. The current study investigated the neuroprotective effects of lentivirus (LV)-mediated C3 transgene expression on rat retinal I/R injury. MAIN METHODS: The LV encoding C3 and green fluorescent protein (GFP) together (LV-C3-GFP) or GFP only (LV-GFP) was intravitreally injected to SPRAGUE-DAWLEY rats. On day 5 post-intravitreal injection, eyes were evaluated by slit-lamp examination. The GFP expression on retina was confirmed by in vivo and ex vivo assessments. RhoA GTPase expression in retina was examined by western blot. Retinal I/R injury was generated by transiently increasing intraocular pressure (110 mmHg, 90 min). Eyes were then enucleated, and retinas processed for morphological analysis and TdT-dUTP terminal nick-end labeling (TUNEL) assay. KEY FINDINGS: No obvious inflammatory reactions or surgical complications were observed after intravitreal injection of LV vectors. There was a significant decrease of total RhoA GTPase level in the retina treated with LV-C3-GFP. Compared to the blank control group, LV-C3-GFP and LV-GFP did not affect the retinal thickness, cell density in ganglion cell layer (GCL), or numbers of apoptotic cells in retinal flat-mounts. In the LV-GFP-treated retinas, I/R decreased the retinal thickness and GCL cell density and increased apoptotic retinal cell numbers. LV-C3-GFP significantly protected against all these degenerative effects of I/R. SIGNIFICANCE: This study indicated that LV-mediated C3 transgene expression exhibits neuroprotective effects on the retinal I/R injury and holds potential as a novel neuroprotective approach targeting certain retinopathies.

Tyrosine triple mutated AAV2-BDNF gene therapy in an inner retinal injury model induced by intravitreal injection of N-methyl-D-aspartate (NMDA).

Purpose: Glaucoma is a group of chronic optic neuropathies characterized by the degeneration of retinal ganglion cells (RGCs) and their axons, and they ultimately cause blindness. Because neuroprotection using neurotrophic factors against RGC loss has been proven a beneficial strategy, extensive attempts have been made to perform gene transfer of neurotrophic proteins. This study used the inner retinal injury mouse model to evaluate the neuroprotective effect of tyrosine triple mutated and self-complementary adeno-associated virus (AAV) encoding brain-derived neurotrophic factor (BDNF; tm-scAAV2-BDNF). Methods: C57BL/6J mice were intravitreally injected with 1 µl of tm-scAAV2-BDNF and its control AAV at a titer of 6.6 E+13 genome copies/ml. Three weeks later, 1 µl of 2 mM N-methyl-D-aspartate (NMDA) was administered in the same way as the viral injection. Six days after the NMDA injection, we assessed the dark-adapted electroretinography (ERG). Mice were sacrificed at one week after the NMDA injection, followed by RNA quantification, protein detection, and histopathological analysis. Results: The RNA expression of BDNF in retinas treated with tm-scAAV2-BDNF was about 300-fold higher than that of its control AAV. Meanwhile, the expression of recombinant BDNF protein increased in retinas treated with tm-scAAV2-BDNF. In addition, histological analysis revealed that tm-scAAV2-BDNF prevented thinning of the inner retina. Furthermore, b-wave amplitudes of the tm-scAAV2-BDNF group were significantly higher than those of the control vector group. Histopathological and electrophysiological evaluations showed that tm-scAAV2-BDNF treatment offered significant protection against NMDA toxicity. Conclusions: Results showed that tm-scAAV2-BDNF-treated retinas were resistant to NMDA injury, while retinas treated with the control AAV exhibited histopathological and functional changes after the administration of NMDA. These results suggest that tm-scAAV2-BDNF is potentially effective against inner retinal injury, including normal tension glaucoma.

Room temperature shipment does not affect the biological activity of pluripotent stem cell-derived retinal organoids.

The generation of laminated and light responsive retinal organoids from induced pluripotent stem cells (iPSCs) provides a powerful tool for the study of retinal diseases and drug discovery and a robust platform for cell-based therapies. The aim of this study is to investigate whether retinal organoids can retain their morphological and functional characteristics upon storage at room temperature (RT) conditions and shipment by air using a commercially available container that maintains the environment at ambient temperature. Morphological analysis and measurements of neuroepithelial thickness revealed no differences between control, RT incubated and shipped organoids. Similarly immunohistochemical analysis showed no differences in cell type composition and position within the laminated retinal structure. All groups showed a similar response to light, suggesting that the biological function of retinal organoids was not affected by RT storage or shipment. These findings provide an advance in transport of ready-made retinal organoids, increasing their availability to many research and pharma labs worldwide and facilitating cross-collaborative research.

Ocular abnormalities in beta thalassemia patients: prevalence, impact, and management strategies.

BACKGROUND: Beta thalassemia (ß-thalassemia) is a hereditary disease caused by defective globin synthesis and can be classified into three categories of minor (ß-TMi), intermedia (ß-TI), and major (ß-TM) thalassemia. The aim of our study is to investigate the effects of ß-thalassemia and its treatment methods on different parts of the eye and how early-diagnostic methods of ocular complications in this disorder would prevent further ocular complications in these patients by immediate treatment and diet change. METHODS: We developed a search strategy using a combination of the words Beta thalassemia, Ocular abnormalities, Iron overload, chelation therapy to identify all articles from PubMed, Web of Science, Scopus, and Google Scholar up to December 2018. To find more articles and to ensure that databases were thoroughly searched, the reference lists of selected articles were also reviewed. RESULTS: Complications such as retinopathy, crystalline lens opacification, color vision deficiency, nyctalopia, depressed visual field, reduced visual acuity, reduced contrast sensitivity, amplitude reduction in a-wave and b-wave in Electroretinography (ERG), and decrease in the Arden ratio in Electrooculography (EOG) have all been reported in ß-thalassemia patients undergoing chelation therapy. CONCLUSION: Ocular problems due to ß-thalassemia may be a result of anemia, iron overload in the body tissue, side effects of iron chelators, and the complications of orbital bone marrow expansion.

Management of Deep Retinal Capillary Ischemia by Electromagnetic Stimulation and Platelet-Rich Plasma: Preliminary Clinical Results.

INTRODUCTION: To investigate the efficacy of retinal electromagnetic stimulation and sub-tenon autologous platelet-rich plasma in the treatment of deep retinal capillary ischemia. METHODS: The study included 28 eyes of 17 patients aged 15-76 years (mean 37.9 years) who had deep retinal capillary ischemia. Patients who had acute-onset paracentral scotoma in the last 1 month were included in the study between January 2018 and January 2019. The diagnosis of deep retinal capillary ischemia was based on clinical history and typical findings of optical coherence tomography angiography. The eyes were divided into three groups: group 1 (n = 7 eyes) received electromagnetic stimulation alone; group 2 (n = 7 eyes) received electromagnetic stimulation and sub-tenon autologous platelet-rich plasma injection; group 3 had no intervention and served as a control group (n = 14 eyes). The patients underwent ten sessions of electromagnetic stimulation in groups 1 and 2. Sub-tenon autologous platelet-rich plasma injection was performed immediately after the first, fifth, and tenth sessions of electromagnetic stimulation in group 2. The deep retinal capillary density and best corrected visual acuity changes were investigated before and after treatment at the first month. RESULTS: The mean deep retinal capillary density was 52.0% before electromagnetic stimulation and 56.1% after ten sessions of application in group 1; this improvement was statistically significant (p = 0.01). In the combined treatment group (group 2), the mean deep retinal capillary density was 46.9% before the treatment and 56.5% after the treatment; this increase was also statistically significant (p = 0.01). Statistically significant best corrected visual acuity improvement (p = 0.01) could be achieved only in group 2. The combined treatment was significantly superior (p < 0.01) to treatment with only electromagnetic stimulation regarding best corrected visual acuity and deep retinal capillary density. In the control group (group 3), there was no statistically significant change (p = 0.09) in the mean deep retinal capillary density and best corrected visual acuity. CONCLUSION: Treatment of the underlying cause is a priority in the treatment of deep retinal capillary ischemia. However, in the acute period, local ischemia treatment is necessary to prevent permanent retinal damage and scotomas. In mild cases, only electromagnetic stimulation, which is non-invasive and easy to use, might have a beneficial effect on deep retinal capillary density. In more severe cases, sub-tenon fresh autologous platelet-rich plasma injection together with electromagnetic stimulation may be more effective in the treatment of local ischemia of the retina in order to augment the response. FUNDING: The Rapid Service Fees were funded by the Ankara University Tecnopolis Institute. CLINICAL TRIAL REGISTRATION: titck.gov.tr identifier, 2018-136.

[Clinical analysis of juxtapapillary retinal capillary hemangioma].

Objective: To discuss the clinical features and treatment of juxtapapillary retinal capillary hemangioma (JRCH). Methods: Retrospective study of the clinical data of 6 patients (7 eyes) who were diagnosed with JRCH, among which 2 eyes were treated by laser therapy (thermotherapy TTT or photodynamic therapy PDT), 2 eyes were treated by intravitreal anti-VEGF injection, 2 eyes with vitreous hemorrhage were treated with vitrectomy (PPV)+ anti-VEGF, and 1 eye was untreated. Results: In the 6 cases, the gender ratio of male to female is 2∶1 with average age of 46 years. Four eyes were associated with macular edema(57.1%), vitreous hemorrhage(n=2, 28.6%), and epiretinal membrane(n=1, 14.2%) in the initial examination. Three patients were associated with von Hippel-Lindau(VHL). During the follow-up period, the visual acuity of the 2 patients treated by TTT decreased. Among the 2 eyes treated by anti-VEGF, the visual acuity of 1 eye associated with macular edema increased, and the visual acuity of 1 eye with macular epiretinal membrane did not change significantly, the visual acuity of both 2 eyes treated by PPV+anti-VEGF improved, the vision of the 1 eye untreated appeared to be stable. Conclusions: Juxtapapillary retinal capillary hemangioma is the orange or red vascular hamartomas that occur on or adjacent to the optic nerve head. It is often associated with macular edema, vitreous hemorrhage, and local subretinal effusion. Symptomatic treatment of complications can effectively improve the visual acuity of patients, while long-term follow-up observation should be organized for patients without complications, laser treatment appears to be ineffective. (Chin J Ophthalmol, 2019, 55:609-615).

Oxalosis Associated With High-Dose Vitamin C Ingestion in a Peritoneal Dialysis Patient.

We report a case of systemic oxalosis involving the eyes and joints due to long-term use of high-dose vitamin C in a patient receiving maintenance peritoneal dialysis (PD). This 76-year-old woman with autosomal dominant polycystic kidney disease underwent living unrelated kidney transplantation 10 years earlier. The transplant failed 6 months before presentation, and she initiated hemodialysis therapy before transitioning to PD therapy 4 months later. During the month before presentation, the patient noted worsening arthralgias and decreased vision. Ophthalmologic examination revealed proliferative retinopathy and calcium oxalate crystals. Plasma oxalate level was markedly elevated at 187 (reference range, <1.7) µmol/L, and urine oxalate-creatinine ratio was high (0.18mg/mg). The patient reported taking up to 4g of vitamin C per day for several years. Workup for causes of primary and secondary hyperoxaluria was otherwise negative. Vitamin C use was discontinued, and the patient transitioned to daily hemodialysis for 2 weeks. Plasma oxalate level before the dialysis session decreased but remained higher (30-53µmol/L) than typical for dialysis patients. Upon discharge, the patient remained on thrice-weekly hemodialysis therapy with stabilized vision and improved joint symptoms. This case highlights the risk of high-dose vitamin C use in patients with advanced chronic kidney disease, especially when maintained on PD therapy.

A simulation tool for better management of retinal services.

BACKGROUND: Advances in the management of retinal diseases have been fast-paced as new treatments become available, resulting in increasing numbers of patients receiving treatment in hospital retinal services. These patients require frequent and long-term follow-up and repeated treatments, resulting in increased pressure on clinical workloads. Due to limited clinic capacity, many National Health Service (NHS) clinics are failing to maintain recommended follow-up intervals for patients receiving care. As such, clear and robust, long term retinal service models are required to assess and respond to the needs of local populations, both currently and in the future. METHODS: A discrete event simulation (DES) tool was developed to facilitate the improvement of retinal services by identifying efficiencies and cost savings within the pathway of care. For a mid-size hospital in England serving a population of over 500,000, we used 36 months of patient level data in conjunction with statistical forecasting and simulation to predict the impact of making changes within the service. RESULTS: A simulation of increased demand and a potential solution of the 'Treat and Extend' (T&E) regimen which is reported to result in better outcomes, in combination with virtual clinics which improve quality, effectiveness and productivity and thus increase capacity is presented. Without the virtual clinic, where T&E is implemented along with the current service, we notice a sharp increase in the number of follow-ups, number of Anti-VEGF injections, and utilisation of resources. In the case of combining T&E with virtual clinics, there is a negligible (almost 0%) impact on utilisation of resources. CONCLUSIONS: Expansion of services to accommodate increasing number of patients seen and treated in retinal services is feasible with service re-organisation. It is inevitable that some form of initial investment is required to implement service expansion through T&E and virtual clinics. However, modelling with DES indicates that such investment is outweighed by cost reductions in the long term as more patients receive optimal treatment and retain vision with better outcomes. The model also shows that the service will experience an average of 10% increase in surplus capacity.

Use of hyperbaric oxygen therapy in quinine-associated visual disturbances.

INTRODUCTION: Hyperbaric oxygen (HBO2 ) therapy is infrequently reported as a treatment for poison-induced retinal damage. We describe a case in which HBO2 therapy was used to treat suspected retinal toxicity induced by quinine. CASE REPORT: We present a case in which HBO2 was used to treat visual disturbances thought to be caused by quinine-induced retinal damage. The patient intentionally ingested undisclosed amounts of citalopram and quinine. Following a complicated hospital course, including profound shock requiring treatment with four vasopressors and a peripheral left-ventricular assist device, the patient, once extubated, reported visual abnormalities consistent with those described from quinine-induced retinal toxicity. Visual disturbances seemed to show improvement following HBO2 treatment. Several months following hospitalization visual defects continued to be present on examination. However, with corrective lenses the patient's visual acuity was normal. No adverse events were attributed to the use of HBO2. DISCUSSION: HBO2 for treatment of quinine-induced retinal damage is infrequently reported or studied. In the reported case, use of HBO2 appeared to be associated with substantial improvement in visual disturbances occurring in the setting of an overdose of quinine. The patient's improvement is remarkable, given her retinas were also jeopardized by her profound shock. Additional data are needed to understand the risks and benefits of this procedure, but due to limited treatment options for poison-induced retinal toxicity and the low likelihood for implementation of a controlled randomized trial of HBO2 in this population, the procedure may be considered in quinine-induced retinal toxicity.

Modeling Retinal Diseases Using Genetic Approaches in Mice.

Genetic mouse models mimicking human diseases have been developed and utilized for retinal research in various topics, involving anatomy, physiology, biochemistry, and pathology. The main reasons why mouse models are important for retinal research include that rodents share a key retinal homology with humans and that genetic manipulation is relatively easily applicable for mice. Here, we describe genetic mouse models, which are categorized with functions in the retina and relationship with human diseases.

Neuroprotective strategies for retinal disease.

Diseases that affect the eye, including photoreceptor degeneration, diabetic retinopathy, and glaucoma, affect 11.8 million people in the US, resulting in vision loss and blindness. Loss of sight affects patient quality of life and puts an economic burden both on individuals and the greater healthcare system. Despite the urgent need for treatments, few effective options currently exist in the clinic. Here, we review research on promising neuroprotective strategies that promote neuronal survival with the potential to protect against vision loss and retinal cell death. Due to the large number of neuroprotective strategies, we restricted our review to approaches that we had direct experience with in the laboratory. We focus on drugs that target survival pathways, including bile acids like UDCA and TUDCA, steroid hormones like progesterone, therapies that target retinal dopamine, and neurotrophic factors. In addition, we review rehabilitative methods that increase endogenous repair mechanisms, including exercise and electrical stimulation therapies. For each approach, we provide background on the neuroprotective strategy, including history of use in other diseases; describe potential mechanisms of action; review the body of research performed in the retina thus far, both in animals and in humans; and discuss considerations when translating each treatment to the clinic and to the retina, including which therapies show the most promise for each retinal disease. Despite the high incidence of retinal diseases and the complexity of mechanisms involved, several promising neuroprotective treatments provide hope to prevent blindness. We discuss attractive candidates here with the goal of furthering retinal research in critical areas to rapidly translate neuroprotective strategies into the clinic.

Potential of Gene Editing and Induced Pluripotent Stem Cells (iPSCs) in Treatment of Retinal Diseases.

The advent of gene editing has introduced the ability to make changes to the genome of cells, thus allowing for correction of genetic mutations in patients with monogenic diseases. Retinal diseases are particularly suitable for the application of this new technology because many retinal diseases, such as Stargardt disease, retinitis pigmentosa (RP), and Leber congenital amaurosis (LCA), are monogenic. Moreover, gene delivery techniques such as the use of adeno-associated virus (AAV) vectors have been optimized for intraocular use, and phase III trials are well underway to treat LCA, a severe form of inherited retinal degeneration, with gene therapy. This review focuses on the use of gene editing techniques and another relatively recent advent, induced pluripotent stem cells (iPSCs), and their potential for the study and treatment of retinal disease. Investment in these technologies, including overcoming challenges such as off-target mutations and low transplanted cell integration, may allow for future treatment of many debilitating inherited retinal diseases.

Efficacy of Purtscher's Retinopathy Treatments: A Systematic Review.

OBJECTIVE: The aim of this review is to evaluate the efficacy of available Purtscher's Retinopathy treatments. MATERIALS AND METHODS: In order to collect single-case reports, electronic searches were conducted in several databases including PubMed, Embase, Web of Science, China National Knowledge Infrastructure, SinoMed, VIP, and WanFang in the Electronic Theses and Dissertations Center. In VIP and Wanfang, we also traced the references of included articles. Risk of bias was evaluated using a tool adapted from the Cochrane Risk of Bias Tool. Statistical analysis was done in SPSS19.0. Evidence was evaluated and graded with GRADE system. RESULTS: In total, 76 studies were included involving 88 cases and 139 eyes. Serious bias existed in 90% of the included studies. Current treatments for Purtscher's retinopathy included glucocorticoid therapy (63.29%), traditional Chinese medicine therapy (10.13%), glucocorticoid integrative medicine therapy (7.60%), and integrative medicine therapy (6.33%). Patients' eyesight with (56.83%) or without (43.17%) treatment both improved in the follow-up within 1-3 months, 4-6 months, and more than 6 months; however, conditions without treatment became better compared to the treatment groups in after 4-6 months and more than 6 months. All results were "very low" in the GRADE system. None of the studies reported adverse reactions in any patient. CONCLUSIONS: Both treatment and no treatment improve vision in Purtscher's retinopathy patients, but the difference between no treatment and glucocorticoid therapy had no statistical significance. The evidence quality for this conclusion was "very low" and had large bias. Further research is required to understand the safety of Purtscher's retinopathy treatment.

Collaborative care of non-urgent macular disease: a study of inter-optometric referrals.

PURPOSE: Diseases involving the macula and posterior pole are leading causes of visual impairment and blindness worldwide and may require prompt ophthalmological care. However, access to eye-care and timely patient management may be limited due to inefficient and inappropriate referrals between primary eye-care providers and ophthalmology. Optometrists with a special interest in macular disease may be useful as a community aid to better stratify and recommend best-practice management plans for suitable patients. This study assesses such a notion by appraising the optometric referral patterns of patients with suspected macular disease to an intermediate-tier optometric imaging clinic. METHODS: We performed a retrospective review of patient records and referrals using patients examined at Centre for Eye Health (CFEH) for an initial or follow up macular assessment between the 1/7/2013 and 30/6/2014 (n = 291). The following data were analysed: patient demographic characteristics, primary reason for referral, diagnosed/suspected condition, CFEH diagnosis and recommended management plan. RESULTS: The number of referrals stipulating a diagnosis, confirmed after evaluation at CFEH was 121 of 291 (42%). After evaluation at CFEH, the number of cases without a specific diagnosis was approximately halved (reduced from 47% to 23%), while the number of cases with no apparent defect or normal aging changes rose from 1% to 15%. Overall diagnostic congruency for specified macular conditions was high (58-94%); cases were seldom (30/291, 10%) found to have a completely different macular condition. 244 of 291 (84%) patients seen at CFEH were recommended ongoing optometric care: either with the referring optometrist or through recall to CFEH. Referral to an ophthalmologist was recommended in 47 instances (16%). CONCLUSIONS: More widespread adoption of intermediate-tier optometric eye-care referral pathways in macular disease (following opportunistic primary care screening) has the potential to reduce the number of cases with non-specific diagnoses and to increase those with a diagnosis of normal aging changes or no apparent disease. The majority of cases seen under this intermediate-tier model required ongoing optometric care only and did not require face-to-face consultation with an ophthalmologist.

Electrical Stimulation as a Means for Improving Vision.

Evolving research has provided evidence that noninvasive electrical stimulation (ES) of the eye may be a promising therapy for either preserving or restoring vision in several retinal and optic nerve diseases. In this review, we focus on minimally invasive strategies for the delivery of ES and accordingly summarize the current literature on transcorneal, transorbital, and transpalpebral ES in both animal experiments and clinical studies. Various mechanisms are believed to underlie the effects of ES, including increased production of neurotrophic agents, improved chorioretinal blood circulation, and inhibition of proinflammatory cytokines. Different animal models have demonstrated favorable effects of ES on both the retina and the optic nerve. Promising effects of ES have also been demonstrated in clinical studies; however, all current studies have a lack of randomization and/or a control group (sham). There is thus a pressing need for a deeper understanding of the underlying mechanisms that govern clinical success and optimization of stimulation parameters in animal studies. In addition, such research should be followed by large, prospective, clinical studies to explore the full potential of ES. Through this review, we aim to provide insight to guide future research on ES as a potential therapy for improving vision.

Bilberry extracts are not created equal: the role of non anthocyanin fraction. Discovering the "dark side of the force" in a preliminary study.

OBJECTIVE: Several experimental studies and clinical trials support the potential of bilberry (Vaccinium myrtillus L) extracts in promoting eye health and circulation. Many active ingredients have been isolated from the berries and leaves of the bilberry plant. However, anthocyanins represent the most widely studied bioactive compounds in this plant. PATIENTS AND METHODS: The aim of this registry, supplement study was to evaluate the effects of Mirtoselect® (standardized in 36% anthocyanins and obtained by an industrial extraction process that preserves the full range of the non-anthocyanin components, mainly natural sugars and polyphenols) in different types of retinal vasculopathies. In total, 140 patients with different types of retinopathy spontaneously decided to join one of the following groups: standard management (SM) only (n=38); SM associated with Mirtoselect® supplementation (n=47); SM associated with a generic bilberry extract supplementation (n=55). Retinal circulatory parameters and flow measurements of the retinal vessels were evaluated at the inclusion and after 6-months supplementation. RESULTS: Overall, significant improvements in several retinal circulatory parameters such as retinal blood flow velocity, with respect to the values at inclusion, were observed in both supplementation groups, especially in Mirtoselect® supplementation group. However, at 6 months, inter-group comparison revealed a statistical advantage in all tested parameters for Mirtoselect® supplementation groups. No side effects or tolerability concerns were reported. CONCLUSIONS: Our registry study suggests that Mirtoselect® supplementation could represent an effective and safe integrated approach for the treatment of different retinopathies.