Detecting Apoptosis as a Clinical Endpoint for Proof of a Clinical Principle

The transparent eye media represent a window through which to observe changes occurring in the retina during pathological processes. In contrast to visualising the extent of neurodegenerative damage that has already occurred, imaging an active process such as apoptosis has the potential to report on disease progression and therefore the threat of irreversible functional loss in various eye and brain diseases. Early diagnosis in these conditions is an important unmet clinical need to avoid or delay irreversible sight loss. In this setting, apoptosis detection is a promising strategy with which to diagnose, provide prognosis and monitor therapeutic response. Additionally, monitoring apoptosis in vitro and in vivo has been shown to be valuable for drug development in order to assess the efficacy of novel therapeutic strategies both in the pre-clinical and clinical setting. Detection of Apoptosing Retinal Cells (DARC) technology is to date the only tool of its kind to have been tested in clinical trials, with other new imaging techniques under investigation in the fields of neuroscience, ophthalmology and drug development. We summarise the transitioning of techniques detecting apoptosis from bench to bedside, along with the future possibilities they encase

Persistent or Recurrent Diabetic Macular Edema After Fluocinolone Acetonide 0.19 mg Implant: Risk Factors and Management

Purpose: To investigate baseline characteristics of patients undergoing additional antivascular endothelial growth factor (VEGF) injections for residual or recurrent diabetic macular edema (DME) in the first year after 0.19-mg fluocinolone acetonide (FAc) implant. Design: Prospective cohort study. Methods: Ninety-four eyes of 66 patients received an FAc implant. Eyes with persistent or recurrent DME were managed with pro re nata anti-VEGF agents. Demographic data and medical history were collected at baseline. Best-corrected visual acuity and central macular thickness were measured every 2 months. The 3 outcomes explored were 1) the risk factors for administration of additional anti-VEGF agents, 2) the interval from FAc to first anti-VEGF injection; and 3) the number of anti-VEGF doses required to maintain regression of DME. Results: Eighteen eyes (19.1%) of 13 patients received 1.3 ± 0.6 anti-VEGF injections. These eyes had significantly thicker central macular thickness at baseline and over the entire follow-up period (P < .001); best-corrected visual acuity was similar at every time point to eyes that were not receiving extra DME treatments. Eyes without preexistent panretinal photocoagulation (PRP) had a higher risk to undergo supplemental treatments (hazard ratio 1.5 [95% confidence interval 1.1-2.5, P = .03). The interval between FAc implant and the first anti-VEGF had a significant linear positive relationship with the number of dexamethasone implants before FAc implant (P = .002, R2 = 0.47). No association was found between baseline factors and the number of injections given. Conclusion: Anti-VEGF agents are efficient treatment to maintain visual acuity in residual/recurrent DME after FAc. Patients with higher baseline central macular thickness and with no previous central macular thickness are more likely to require additional treatments to control DME

Personalized approaches for the management of glaucoma

Introduction: Personalized medicine is the future goal across all specialties. Accurate prediction of optimal treatment beneficial and adverse effects could transform patient management. This is of particular importance in chronic conditions, where a ‘trial and error’ approach over months and years can contribute to significant morbidity. Glaucoma is a chronic irreversible progressive optic neuropathy, a leading cause of blindness worldwide. An ideal personalized approach in glaucoma clinic would be to answer the inevitable question in a patient’s first visit: ‘Which treatment option will work best for me so that I won’t go blind?’ / Areas covered: This review will give an overview of the knowledge we have acquired to achieve this goal, particularly discussing using patient’s individual risk factors, their genetic profile, and different treatment modalities, including therapy compliance, to personalize care. / Expert opinion: Pharmacogenomics and genetic profiling are the most tangible ways in which glaucoma management can be personalized. Future challenges will include developing realistic animal models to reflect the underlying genetic patterns in glaucoma to investigate their interaction with different treatments

Correction: The outcome of fluocinolone acetonide intravitreal implant is predicted by the response to dexamethasone implant in diabetic macular oedema (Eye, (2021), 35, 12, (3232-3242), 10.1038/s41433-020-01373-1)

A Correction to this paper has been published: https://doi.org/10.1038/s41433-021-01469-2

The outcome of fluocinolone acetonide intravitreal implant is predicted by the response to dexamethasone implant in diabetic macular oedema

Background/Objectives: To investigate if the visual and anatomic response to the first dexamethasone implant (DEX) predicts the 12-month clinical outcome after shifting to fluocinolone acetonide (FAc) implant in patients with diabetic macular oedema (DMO). Methods: Retrospective cohort study including pseudophakic patients with previously treated DMO, undergone one or more DEX injections before FAc. Functional and morphologic response to DEX was defined based on the best-corrected visual acuity (BCVA) and central macular thickness (CMT) changes after the first DEX, respectively. Steroid-response was defined as intraocular pressure (IOP) elevation ≥5 mmHg or IOP > 21 mmHg after any previous DEX exposure. Pairwise comparisons for BCVA, CMT, and IOP after FAc were performed with linear mixed models and a repeated-measure design. Results: Forty-four eyes of 33 patients were included. Patients were shifted to FAc after a mean ± standard deviation of 4.6 ± 3.2 DEX injections. Overall, BCVA and CMT improved during the first 12 months after switching to FAc (p = 0.04 and p < 0.001, respectively). Only eyes with a good morphologic response to DEX had a significant CMT reduction after FAc (p < 0.001), while no significant relationship was found between BCVA improvement after DEX and after FAc. IOP elevation occurred in 9 eyes (20%) following DEX implant. These eyes carried a 20-fold increased risk of having an IOP rise after FAc (p < 0.001), with a non-linear relationship between the IOP increase after DEX and the one after FAc. Conclusion: The response to previous DEX may anticipate the morphologic response to subsequent FAc. Eyes with steroid-induced IOP elevation after DEX are at a high risk of IOP increase after FAc. The visual response after FAc was not associated with the visual response to previous steroids, indicating that FAc may have a role also in patients refractory to DEX implant

The outcome of fluocinolone acetonide intravitreal implant is predicted by the response to dexamethasone implant in diabetic macular oedema

Background/Objectives: To investigate if the visual and anatomic response to the first dexamethasone implant (DEX) predicts the 12-month clinical outcome after shifting to fluocinolone acetonide (FAc) implant in patients with diabetic macular oedema (DMO). Methods: Retrospective cohort study including pseudophakic patients with previously treated DMO, undergone one or more DEX injections before FAc. Functional and morphologic response to DEX was defined based on the best-corrected visual acuity (BCVA) and central macular thickness (CMT) changes after the first DEX, respectively. Steroid-response was defined as intraocular pressure (IOP) elevation ≥5 mmHg or IOP &gt; 21 mmHg after any previous DEX exposure. Pairwise comparisons for BCVA, CMT, and IOP after FAc were performed with linear mixed models and a repeated-measure design. Results: Forty-four eyes of 33 patients were included. Patients were shifted to FAc after a mean ± standard deviation of 4.6 ± 3.2 DEX injections. Overall, BCVA and CMT improved during the first 12 months after switching to FAc (p = 0.04 and p &lt; 0.001, respectively). Only eyes with a good morphologic response to DEX had a significant CMT reduction after FAc (p &lt; 0.001), while no significant relationship was found between BCVA improvement after DEX and after FAc. IOP elevation occurred in 9 eyes (20%) following DEX implant. These eyes carried a 20-fold increased risk of having an IOP rise after FAc (p &lt; 0.001), with a non-linear relationship between the IOP increase after DEX and the one after FAc. Conclusion: The response to previous DEX may anticipate the morphologic response to subsequent FAc. Eyes with steroid-induced IOP elevation after DEX are at a high risk of IOP increase after FAc. The visual response after FAc was not associated with the visual response to previous steroids, indicating that FAc may have a role also in patients refractory to DEX implant. © 2021, The Author(s), under exclusive licence to The Royal College of Ophthalmologists

Pinger affects fish catch efficiency and damage to bottom gill nets related to bottlenose dolphins

There is some evidence that the presence of Tursiops truncatus in fishing areas represents a real economic threat to fishermen due the dolphin feeding on the entangled fish, damaging the nets and reducing the fish catch. We have carried out experiments to assess the efficiency of a pinger in decreasing the interaction between the dolphins and fishing nets, in a fishing area off the coast of southern Italy, where Tursiops truncatus is frequently observed to interact with bottom gill nets. Two identical monofilament bottom gill nets (900 m long), one equipped with pingers and the other without, were used to measure the effect of these pingers on the abundance of the catch and net damage. For each haul (58 in total), data on dolphin sightings near the nets, damage judged to have been doneby dolphins, weight and species composition of the catch were collected. All damage to the nets were recorded at the end of each haul. Dolphins in the fishing area were sighted 11 times out of 29 fishing activities (38%). The net equipped with pingers contained 28% more fish (biomass) than the net without pingers (t test, P\0.04) and was less damaged (-31%, t test, P\0.01). To assess whether the efficacy of these pingers remain constant over long period, long-term experiments should be carried out