Analysis of optical coherence tomography biomarker probability detection in central serous chorioretinopathy by using an artificial intelligence-based biomarker detector.

AIM: To adopt a novel artificial intelligence (AI) optical coherence tomography (OCT)-based program to identify the presence of biomarkers associated with central serous chorioretinopathy (CSC) and whether these can differentiate between acute and chronic central serous chorioretinopathy (aCSC and cCSC). METHODS: Multicenter, observational study with a retrospective design enrolling treatment-naïve patients with aCSC and cCSC. The diagnosis of aCSC and cCSC was established with multimodal imaging and for the current study subsequent follow-up visits were also considered. Baseline OCTs were analyzed by an AI-based platform (Discovery® OCT Fluid and Biomarker Detector, RetinAI AG, Switzerland). This software allows to detect several different biomarkers in each single OCT scan, including subretinal fluid (SRF), intraretinal fluid (IRF), hyperreflective foci (HF) and flat irregular pigment epithelium detachment (FIPED). The presence of SRF was considered as a necessary inclusion criterion for performing biomarker analysis and OCT slabs without SRF presence were excluded from the analysis. RESULTS: Overall, 160 eyes of 144 patients with CSC were enrolled, out of which 100 (62.5%) eyes were diagnosed with cCSC and 60 eyes (34.5%) with aCSC. In the OCT slabs showing presence of SRF the presence of biomarkers was found to be clinically relevant (> 50%) for HF and FIPED in aCSC and cCSC. HF had an average percentage of 81% (± 20) in the cCSC group and 81% (± 15) in the aCSC group (p = 0.4295) and FIPED had a mean percentage of 88% (± 18) in cCSC vs. 89% (± 15) in the aCSC (p = 0.3197). CONCLUSION: We demonstrate that HF and FIPED are OCT biomarkers positively associated with CSC when present at baseline. While both HF and FIPED biomarkers could aid in CSC diagnosis, they could not distinguish between aCSC and cCSC at the first visit. AI-assisted biomarker detection shows promise for reducing invasive imaging needs, but further validation through longitudinal studies is needed.

Iris Reconstruction: A Surgeon's Guide.

Objectives: The aim of this review paper is to summarise surgical options available for repairing iris defects at the iris-lens plane, focusing on suturing techniques, iridodialysis repair, and prosthetic iris devices. Methods: A thorough literature search was conducted using multiple databases, including Medline, PubMed, Web of Science Core Collection, and the Cochrane Library, from inception to February 2024. Relevant studies were screened based on predefined criteria, and primary references cited in selected articles were also reviewed. Results: Various surgical techniques were identified for iris defect repair. Suturing methods such as interrupted full-thickness sutures and the McCannel technique offer solutions for smaller defects, while iridodialysis repair techniques address detachment of the iris from the ciliary body. Prosthetic iris devices, including iris-lens diaphragm devices, endocapsular capsular tension ring-based devices, and customizable artificial iris implants, provide options for larger defects, each with its own advantages and limitations. Conclusions: Successful iris reconstruction requires a personalised approach considering factors like defect size, ocular comorbidities, and patient preference. Surgeons must possess a thorough understanding of available techniques and prosthetic devices to achieve optimal outcomes in terms of both visual function and, nonetheless, cosmetic appearance.

Perspectives on the currently available pharmacotherapy for wet macular degeneration.

INTRODUCTION: Wet age-related macular degeneration (w-AMD) is a leading cause of visual impairment globally, with its prevalence expected to rise alongside increasing life expectancy. The current standard treatment involves frequent intravitreal injections of anti-VEGF agents, which although revolutionary, pose significant burdens on both patients and healthcare services. AREAS COVERED: This review explores current and emerging pharmaceutical treatments for w-AMD, focusing on their pharmacokinetics, pharmacodynamics, efficacy, and safety. Promising developments include extending treatment intervals with newer anti-VEGF agents like brolucizumab and faricimab, biosimilars offering cost-effective options, and exploring innovative drug delivery methods such as subretinal gene therapy. Combination therapies, gene therapies, and novel agents like KSI-301 and OPT-302 show potential for improving treatment outcomes and reducing treatment burden. EXPERT OPINION: While current treatments for w-AMD have significantly advanced with the advent of anti-VEGF therapies, their limitations in terms of treatment burden and incomplete responses have spurred research into diverse alternative approaches. These innovative strategies offer hope for improving patient outcomes and reducing healthcare burdens, suggesting a promising future for w-AMD management.

Prechoroidal Cleft Regression After Switch to Intravitreal Brolucizumab.

INTRODUCTION: Prechoroidal cleft has been described as a negative prognostic biomarker in patients affected with neovascular age related macular degeneration (nAMD). This peculiar finding consists of a lenticular hyporeflective space located between an outward bowing of Bruch's membrane and the base of a fibrovascular retinal pigment epithelium detachment (PED). Previous studies have reported the partial or complete regression of prechoroidal clefts after treatment with anti-vascular endothelial growth factor (VEGF) injections. CASE REPORT: To report a case of complete anatomical regression of an unresponsive prechoroidal cleft after switching to intravitreal Brolucizumab. The patient maintained cleft regression over time and no adverse events (i.e., RPE tears, intraocular inflammation) were observed during follow-up. CONCLUSIONS AND IMPORTANCE: To our knowledge, this case report is the first to analyze the clinical efficacy of brolucizumab targeting prechoroidal clefts. Clinical implication and pathogenesis of prechoroidal clefts are yet to be fully elucidated.

Proliferative vitreoretinopathy: an update on the current and emerging treatment options.

Proliferative vitreoretinopathy (PVR) remains the main cause of failure in retinal detachment (RD) surgery and a demanding challenge for vitreoretinal surgeons. Despite the large improvements in surgical techniques and a better understanding of PVR pathogenesis in the last years, satisfactory anatomical and visual outcomes have not been provided yet. For this reason, several different adjunctive pharmacological agents have been investigated in combination with surgery. In this review, we analyze the current and emerging adjunctive treatment options for the management of PVR and we discuss their possible clinical application and beneficial role in this subgroup of patients.

BASELINE SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHIC RETINAL LAYER FEATURES IDENTIFIED BY ARTIFICIAL INTELLIGENCE PREDICT THE COURSE OF CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To identify optical coherence tomography (OCT) features to predict the course of central serous chorioretinopathy (CSC) with an artificial intelligence-based program. METHODS: Multicenter, observational study with a retrospective design. Treatment-naïve patients with acute CSC and chronic CSC were enrolled. Baseline OCTs were examined by an artificial intelligence-developed platform (Discovery OCT Fluid and Biomarker Detector, RetinAI AG, Switzerland). Through this platform, automated retinal layer thicknesses and volumes, including intaretinal and subretinal fluid, and pigment epithelium detachment were measured. Baseline OCT features were compared between acute CSC and chronic CSC patients. RESULTS: One hundred and sixty eyes of 144 patients with CSC were enrolled, of which 100 had chronic CSC and 60 acute CSC. Retinal layer analysis of baseline OCT scans showed that the inner nuclear layer, the outer nuclear layer, and the photoreceptor-retinal pigmented epithelium complex were significantly thicker at baseline in eyes with acute CSC in comparison with those with chronic CSC ( P < 0.001). Similarly, choriocapillaris and choroidal stroma and retinal thickness (RT) were thicker in acute CSC than chronic CSC eyes ( P = 0.001). Volume analysis revealed average greater subretinal fluid volumes in the acute CSC group in comparison with chronic CSC ( P = 0.041). CONCLUSION: Optical coherence tomography features may be helpful to predict the clinical course of CSC. The baseline presence of an increased thickness in the outer retinal layers, choriocapillaris and choroidal stroma, and subretinal fluid volume seems to be associated with acute course of the disease.

"Application and accuracy of artificial intelligence-derived large language models in patients with age related macular degeneration".

INTRODUCTION: Age-related macular degeneration (AMD) affects millions of people globally, leading to a surge in online research of putative diagnoses, causing potential misinformation and anxiety in patients and their parents. This study explores the efficacy of artificial intelligence-derived large language models (LLMs) like in addressing AMD patients' questions. METHODS: ChatGPT 3.5 (2023), Bing AI (2023), and Google Bard (2023) were adopted as LLMs. Patients' questions were subdivided in two question categories, (a) general medical advice and (b) pre- and post-intravitreal injection advice and classified as (1) accurate and sufficient (2) partially accurate but sufficient and (3) inaccurate and not sufficient. Non-parametric test has been done to compare the means between the 3 LLMs scores and also an analysis of variance and reliability tests were performed among the 3 groups. RESULTS: In category a) of questions, the average score was 1.20 (± 0.41) with ChatGPT 3.5, 1.60 (± 0.63) with Bing AI and 1.60 (± 0.73) with Google Bard, showing no significant differences among the 3 groups (p = 0.129). The average score in category b was 1.07 (± 0.27) with ChatGPT 3.5, 1.69 (± 0.63) with Bing AI and 1.38 (± 0.63) with Google Bard, showing a significant difference among the 3 groups (p = 0.0042). Reliability statistics showed Chronbach's α of 0.237 (range 0.448, 0.096-0.544). CONCLUSION: ChatGPT 3.5 consistently offered the most accurate and satisfactory responses, particularly with technical queries. While LLMs displayed promise in providing precise information about AMD; however, further improvements are needed especially in more technical questions.

Investigational drugs inhibiting complement for the treatment of geographic atrophy.

INTRODUCTION: Geographic atrophy (GA) is a progressive form of age-related macular degeneration (AMD) that leads to severe visual impairment and central vision loss. Traditional treatment options for GA are limited, highlighting the need for new therapeutic approaches. In recent years, targeting the complement system has emerged as a promising strategy for the treatment of GA. AREAS COVERED: This expert opinion article reviews the investigational drugs inhibiting the complement cascade for the treatment of GA. Specifically, it focuses on the recent FDA approved pegcetacoplan, a C3 complement inhibitor, and avacincaptad pegol, a C5 complement inhibitor, highlighting their potential efficacy and safety profiles based on clinical trial data. EXPERT OPINION: FDA approval of intravitreal pegcetacoplan and avacincaptad pegol marks significant progress in the landscape of GA treatment. However, variable results from trials underscore the complex nature of GA and the importance of patient selection. Complement inhibition holds promise, but ongoing research is vital to refine treatment strategies and offer improved outcomes for GA patients.

Faricimab for the Treatment of Diabetic Macular Edema and Neovascular Age-Related Macular Degeneration.

Nowadays; intravitreal anti-vascular endothelial growth factor (VEGF) drugs are considered the first-line therapeutic strategy for treating macular exudative diseases; including wet age-related macular degeneration (w-AMD) and diabetic macular edema (DME). Despite the important clinical achievements obtained by anti-VEGF drugs in the management of w-AMD and DME; some limits still remain; including high treatment burden; the presence of unsatisfactory results in a certain percentage of patients and long-term visual acuity decline due to complications such as macular atrophy and fibrosis. Targeting the angiopoietin/Tie (Ang/Tie) pathway beyond the VEGF pathway may be a possible therapeutic strategy; which may has the potential to solve some of the previous mentioned challenges. Faricimab is a new; bispecific antibody targeting both VEGF-A and the Ang-Tie/pathway. It was approved by FDA and; more recently; by EMA for treating w-AMD and DME. Results from phase III trials TENAYA and LUCERNE (w-AMD) and RHINE and YOSEMITE (DME) have shown the potential of faricimab to maintain clinical efficacy with more prolonged treatment regimens compared to aflibercept (12 or 16 weeks) with a a good safety profile.

Cenegermin for the treatment of dry eye disease.

Dry eye disease (DED) is the most common ocular surface disorder affecting millions of people worldwide. Due to its chronic nature, the management of DED still represents a challenge in the ophthalmic practice. Nerve growth factor (NGF), which is expressed along with its high-affinity TrkA receptor on the ocular surface complex, has been widely studied for the treatment of neurotrophic keratopathy, and a novel recombinant human NGF (rhNGF) has recently received full market authorization in this setting. Since NGF has shown in both in vitro and in vivo studies to promote corneal healing, to enhance conjunctival epithelium differentiation and mucin secretion, and to stimulate tear film production and functionality, it could provide potential benefits also in patients with DED. A recent phase II clinical trial has assessed the role of rhNGF in DED patients, demonstrating significant improvements of DED signs and symptoms after 4 weeks of treatment. Further clinical evidence will be provided by the 2 ongoing phase III clinical trials. This review aims at comprehensively illustrating the rationale of use along with the efficacy and safety profile of topical NGF in patients with DED.

Multimodal imaging for the management of Lyme-associated uveitis: A case report from an Italian tertiary center.

INTRODUCTION: Lyme borreliosis may present with different systemic manifestations and also the ocular involvement may be difficult to diagnose because of its multifaceted presentation. Considering the growing incidence of Lyme disease in European countries, ophthalmologist should be trained to distinguish ocular borreliosis. CASE REPORT: Several clinical presentations have been previously described, including uveitis, unilateral or bilateral chorioretinitis, keratitis, episcleritis, papillitis and ischemic optic neuropathy, retinal vasculitis and acute posterior multifocal placoid pigment epitheliopathy (APMPPE); however our case report showed a rare presentation with the presence of unilateral uveitis with vitreitis and multiple, patchy, yellowish lesions, in association with retinal vasculitis. This clinical picture was to be considered in differential diagnosis with ocular Toxoplasmosis. CONCLUSIONS: The appropriate management of this patient was made possible by the combination of multimodal imaging and appropriate laboratory tests, representing the optimal process in the diagnostic and therapeutic pathway in high-risk patients for ocular Lyme disease.

Current treatment options for treating OPA1-mutant dominant optic atrophy.

Dominant optic atrophy (DOA) is caused by OPA1 gene mutation, and it represents one of the most frequently diagnosed forms of hereditary optic neuropathies. This neurodegenerative disorder typically occurs in the first decades of life, and it is often associated with severe visual impairment. For this reason, several treatment options have been examined for the management of DOA, including vitamin supplements, ubiquinone analogues (in particular idebenone) and, more recently, gene therapy. Among them, idebenone has shown the most promising clinical outcomes in recent real-life studies. Furthermore, gene therapy represents also a promising therapeutic approach; however, more evidence in clinical trials is needed. In this review, we will summarize and discuss all the possible treatment options for DOA, in order to identify the current optimal management in these patients, whose visual prognosis remains unfortunately poor and unsatisfactory in the everyday clinical practice.

The upcoming role of Artificial Intelligence (AI) for retinal and glaucomatous diseases.

In recent years, the role of artificial intelligence (AI) and deep learning (DL) models is attracting increasing global interest in the field of ophthalmology. DL models are considered the current state-of-art among the AI technologies. In fact, DL systems have the capability to recognize, quantify and describe pathological clinical features. Their role is currently being investigated for the early diagnosis and management of several retinal diseases and glaucoma. The application of DL models to fundus photographs, visual fields and optical coherence tomography (OCT) imaging has provided promising results in the early detection of diabetic retinopathy (DR), wet age-related macular degeneration (w-AMD), retinopathy of prematurity (ROP) and glaucoma. In this review we analyze the current evidence of AI applied to these ocular diseases, as well as discuss the possible future developments and potential clinical implications, without neglecting the present limitations and challenges in order to adopt AI and DL models as powerful tools in the everyday routine clinical practice.

Blood Reflux Through a PreserFlo MicroShunt Device After Needling.

INTRODUCTION: To report a case of hyphema after a bleb needling revision in a PreserFlo MicroShunt implantation. CASE DESCRIPTION: An 87-year-old man suffering from bilateral open angle glaucoma was referred to our hospital with a diagnosis of unsatisfactory intraocular pressure (IOP) control in the right eye, despite the maximally tolerated medical therapy. The patient underwent PreserFlo MicroShunt implantation in his right eye. About 2 months after the surgical procedure, the IOP was raised because of bleb failure for subconjunctival scarring. A needling revision was performed at the slit lamp. During the procedure blood reflux through a PreserFlo MicroShunt device from a filtering bleb to the anterior chamber was observed, causing an IOP rise. Treatment with oral acetazolamide, topical steroid, and antibiotic resulted in the complete resolution of the hyphema in 2 weeks and a significant lowering in IOP. CONCLUSIONS: This is the first reported case of blood reflux to the anterior chamber through a PreserFlo MicroShunt implant after a needling procedure.

Effects of a New Formulation of Multiple-Action Tear Substitute on Objective Ocular Surface Parameters and Ocular Discomfort Symptoms in Patients with Dry Eye Disease.

INTRODUCTION: Recently, there has been a progressive shift from simple water-adding medications towards complex multi-action combined formulas aimed at disrupting different mechanisms within the dry eye disease (DED) vicious cycle. This study evaluated the efficacy and tolerability of Trimix eye drops (Off Health Italia, Italy), a combination of viscosity-enhancing hyaluronic acid, trehalose, and cationic liposomes comprising stearylamine and phospholipids, in patients with DED. METHODS: In this prospective, pilot study patients diagnosed with mild to moderate DED were enrolled and treated with Trimix eye drops three times daily for 2 months. Ocular surface workup was performed before (V0) and after therapy (V1) by means of IDRA (SBM Sistemi, Turin, Italy), for the measurement of (i) noninvasive break-up time (NIBUT); (ii) tear meniscus height (TMH); (iii) lipid layer thickness (LLT); (iv) infrared meibography (percentage of meibomian gland loss); (v) bulbar redness (Efron scale). Treatment tolerability was scored on a visual analog scale ranging from 0 (none/not at all) to 100 (much/very) for eight questions. Ocular discomfort symptoms were scored using the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire. RESULTS: Overall, 25 subjects (mean age 60.32 ± 14.55 years) were included in the study. At V1, TMH, NIBUT, and LLT significantly increased compared to V0 (from 0.29 ± 0.06 to 0.46 ± 0.06 mm, 6.34 ± 2.61 to 7.58 ± 2.52 s, and from 63.26 ± 17.15 to 68.42 ± 15.63 nm, respectively; all P < 0.04). Concerning ocular discomfort symptoms, SPEED score significantly improved at V1 (from 16.63 ± 6.32 to 8.30 ± 5.98; P < 0.001); moreover, treatment tolerability was high for all eight items investigated. CONCLUSIONS: Two-month treatment with Trimix formulation improved objective signs and subjective symptoms in patients with DED, showing also a good tolerability profile.

The Role of Atropine in Preventing Myopia Progression: An Update.

Several approaches have been investigated for preventing myopia progression in children and teenagers. Among them, topical atropine has shown promising results and it is being adopted in clinical practice more and more frequently. However, the optimal formulation and treatment algorithm are still to be determined. We discuss the pharmacokinetic, pharmacodynamic, clinical, and tolerability profile revealed first by the multicenter, randomized ATOM 1 and 2 trials and, more recently, by the LAMP Study. Results from these trials confirmed the efficacy of low-concentration atropine with a concentration-dependent response. Although atropine at 0.025% and 0.05% concentrations has shown the most encouraging results in large-scale studies, these formulations are not yet commonplace in worldwide clinical practice. Moreover, their rebound effect and the possibility of reaching a stabilization effect have not been fully investigated with real-life studies. Thus, further larger-scale studies should better characterize the clinical efficacy of atropine over longer follow-up periods, in order to define the optimal dosage and treatment regimen.

Corneal Findings Associated to Belantamab-Mafodotin (Belamaf) Use in a Series of Patients Examined Longitudinally by Means of Advanced Corneal Imaging.

Belantamab mafodotin (belamaf) is a novel antibody-drug conjugate developed for the treatment of patients with relapsed or refractory multiple myeloma (RRMM). Although the drug has demonstrated a good efficacy, corneal adverse events have been reported. In this prospective study, consecutive patients with RRMM who received belamaf infusions were included. The standard ophthalmological visit was implemented with anterior segment (AS)-optical coherence tomography (OCT) and in vivo confocal microscopy (IVCM). Five patients (three males, two females; mean age 66 ± 6.0 years) with MMRR and unremarkable ocular findings at baseline who received belamaf infusion were included. After a median time of 28 days from the first infusion, four of them developed corneal alterations with transient vision reduction to a variable extent. In particular, corneal deposits of microcyst-like epithelial changes (MECs) were detected centrally in one patient and peripherally in three patients. AS-OCT scans showed a bilateral heterogeneous increase in signal intensity, together with hyper-reflective lesions confined within the epithelium in all cases, except for one case in which they also involved the stroma. Corneal maps showed a transient increase in epithelial thickness in the first phase that was followed by a diffuse decrease in the subsequent phase. IVCM scans showed MECs as hyper-reflective opacities located at the level of corneal epithelium, largely intracellular. Multimodal corneal imaging may implement the current clinical scale, helping us to detect corneal abnormalities in patients under belamaf therapy. This workup provides useful data for monitoring over time corneal findings and for optimizing systemic therapy.

Evaluation of macular vessel density changes after strabismus surgery using optical coherence tomography angiography.

PURPOSE: To compare retinal vessel density before and after strabismus surgery using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: In this longitudinal, single-arm pilot study, vascular density in the deep capillary plexus (DCP), superficial retinal capillary plexus (SCP) and choriocapillaris layer (CCL) in consecutive subjects undergoing strabismus surgery was assessed using SS-OCTA preoperatively (T0), on the first day postoperatively (POD1), and 30 days postoperatively (POD30). RESULTS: A total of 92 eyes of 56 patients (54% males) were included. Mean patient age was 41.1 ± 22.7. OCT vascular density of the DCP was 50.20 ± 5.57 at T0, 52.74 ± 4.77 at POD1, and 50.92 ± 4.58 at POD30. The differences were statistically significant for T0 versus POD1 (P < 0.05). Vascular density of the CCL was 50.72 ± 4.80 at T0, 53.59 ± 3.65 at POD1, and 51.39 ± 4.64 at POD30. The differences were statistically significant for T0 versus POD1 (P < 0.05). No significant differences were found in SCP (P > 0.05). CONCLUSIONS: Transitory hemodynamic changes can occur in the DCP and in the CCL following muscle recession procedures.