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.

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.

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.

The emerging role of the Angiopoietin-Tie pathway as therapeutic target for treating retinal diseases.

INTRODUCTION: Several approaches have been investigated for treating wet age-related macular degeneration (w-AMD), diabetic macular edema (DME) and retinal vein occlusions (RVOs). The first-line treatment for these exudative retinal diseases consists of anti-vascular endothelial growth factor (VEGF) agents; however, the high treatment burden and the percentage of 'non responder' patients have highlighted the need for other approaches. Increasing evidence has shown the role of angiopoietin/Tie (Ang/Tie) pathway in the pathogenesis of these exudative retinal diseases; therefore, novel drugs targeting this pathway are under evaluation in clinical trials. AREAS COVERED: We analyzed the novel, emerging drugs (ARP- 1536, the coformulation of aflibercept and nesvacumab, AXT107 and AKB-9778) that target the Ang/Tie pathway. These drugs are still in early phase clinical trials, but encouraging outcomes have emerged. We also discuss the clinical efficacy of faricimab, a bispecific monoclonal antibody that inhibits VEGF-A and Ang-2. EXPERT OPINION: The simultaneous targeting of the VEGF and Ang/Tie pathways may be more beneficial than monotherapy in patients with exudative retinal diseases. Among the investigational drugs targeting the Ang/Tie pathway, faricimab has shown promising results in phase II/III trials and in the near future may represent a viable treatment option for the management of exudative macular diseases.

Efficacy of a New Commercial Ocular Spray Containing Oftasecur Citrus Extract for Reducing Microbial Load in the Conjunctiva of Patients Receiving Intravitreal Injections.

INTRODUCTION: The control of conjunctival microbial load is crucial for patients receiving intravitreal injections (IVTs) in order to reduce the risk of endophthalmitis. The purpose of this work was to assess the antimicrobial activity of a new commercial ocular spray containing Biosecur citrus extract (Oftasecur®, Off Health, Florence, Italy). METHODS: This prospective cross-sectional pilot study included patients receiving IVTs who were instructed to apply Oftasecur spray onto the eye to be injected four times daily starting 4 days before surgery. The contralateral eye was considered the control. A conjunctival swab for microbiological analysis was performed in both eyes before starting study treatment and at the time of the injection. The Brief Ocular Discomfort Inventory (BODI) questionnaire was administered to patients based on an 11-point scale (0 for no discomfort and 10 for maximum discomfort). RESULTS: Thirty patients (15 male, 15 female; mean age 64.7 ± 11.6 [standard deviation, SD] years) were included. Before starting treatment, 53.3% of the total eyes tested positive during the microbiological analysis. After the treatment period, only 20% of the eyes tested positive at the time of injection, showing a significant reduction in the microbial load (p < 0.01). Moreover, in the treated arm, the positive swabs before and after the prophylactic treatment with Oftasecur ocular spray showed a significant reduction (from 70.4% to 29.6%; p = 0.003, McNemar's test). Oftasecur ocular spray was well tolerated, with an average BODI score of 1.2 (± 0.70 SD). CONCLUSION: Oftasecur ocular spray showed antimicrobial activity that significantly reduced the microbial load in patients receiving intravitreal injections. Therefore, it may have a role in the prophylaxis of infection in the setting of IVTs.

A 2-year prospective multicenter study of ultrasound cyclo plasty for glaucoma.

Ultrasound cyclo plasty (UCP) is a recently developed surgical technique for glaucoma allowing a selective and controlled coagulation of the ciliary body. We herein investigated the long-term efficacy and safety of UCP for the treatment of glaucoma. This prospective study included patients with primary and secondary glaucoma. All surgeries were performed using the EyeOP1 device (Eye Tech Care, Rillieux-la-Pape, France). Sixty-six patients were included, and 60 completed regularly the 2-year follow-up. Preoperative IOP was 28.5 ± 9.6 mmHg and significantly decreased to 17.0 ± 5.4 at 2 years (p < 0.001). The daily number of both hypotensive eye drops and acetazolamide tablets decreased significantly (respectively, from 2.6 ± 1.1 to 1.7 ± 1.2 and from 0.7 ± 0.8 to 0.2 ± 0.5; both p < 0.001). At 2 years, 68.1% of patients met the definition of qualified success (IOP < 21 mmHg regardless of glaucoma medications) and 10.3% of patients met the definition of complete success (IOP < 21 mmHg without glaucoma medications). No major intra- or postoperative complications occurred; however, 15 eyes required additional glaucoma surgery. These results suggest that UCP is an effective and safe procedure to reduce IOP in glaucoma patients through a 2-year follow-up period.

Ocular biometric parameters changes and choroidal vascular abnormalities in patients with neurofibromatosis type 1 evaluated by OCT-A.

PURPOSE: To analyze ocular biometric parameters alterations of the posterior pole and choroidal abnormalities in patients with neurofibromatosis type 1 (NF1) by adopting multimodal imaging, especially focusing on the role of novel diagnostic devices like swept-source optical coherence tomography angiography (SS-OCTA). METHODS: In this prospective, case-controlled study, patients with NF1 and age-matched control subjects were quantitatively analyzed by using multimodal imaging. All the subjects underwent confocal scanning laser ophthalmoscopy (SLO), SS-OCT and SS-OCTA examinations. RESULTS: SS-OCT analysis revealed a lower macular retinal nerve fiber layer (RNFL) thickness in patients with NF1 compared with those with suspected NF1 (95.0±15.9 vs 109.7±11.3 µm; P = 0.001) and control subjects (106.8±14.4 µm, P = 0.003). Retinal thickness was significantly lower in NF1 patients compared to those with suspected NF1 (280.7±23.0 vs 304.2±15.3 µm; P < 0.001) and control subjects (298.7±23.8 µm, P = 0.003). The mean vascular flow area of the SCP was significantly higher in patients with NF1 (42.6±2.2%) and suspected NF1 (43.1±2.5%) compared to control subjects (41.0±2.0%; respectively, P = 0.017 and P = 0.002). In the second choroidal layer, the flow area was significantly lower in patients with NF1 compared to control subjects (45.4±4.8 vs 49.0±4.0%,; P = 0.011). CONCLUSIONS: Retinal thicknesses alterations and choroidal nodules are described as ocular manifestations in patients with NF1. In addition, OCTA could represent an important novel advanced imaging technique, capable of detecting early altered retinal and choroidal vascular flow area in patients with NF1.

Brolucizumab: a novel anti-VEGF humanized single-chain antibody fragment for treating w-AMD.

INTRODUCTION: Wet age-related macular degeneration (w-AMD) represents the leading cause of visual impairment in the elderly in the developed countries. Intravitreal antivascular endothelial growth factor (VEGF) drugs are currently considered as the first-line treatment option for treating w-AMD; however, the frequent injection intervals have lit the way to investigate novel anti-VEGF agents allowing a more extended treatment regimen. Brolucizumab is a single-chain antibody fragment targeting all the isoforms of VEGF-A. Phase III HAWK and HARRIER trials have shown a longer durability and superior anatomical outcomes as compared with the standard of care by adopting a quarterly regimen for treating w-AMD. Brolucizumab has been approved in Europe, USA, and Japan for the management of w-AMD. AREAS COVERED: This article presents an overview of w-AMD and investigates the progress of brolucizumab through clinical trials. It offers insights into where brolucizumab may be placed in the current market of anti-VEGF agents and its potential advantages over the previous molecules adopted for treating w-AMD. EXPERT OPINION: The possibility of administering brolucizumab with more dilated treatment intervals represents an important advantage to decrease the treatment burden and improve patient compliance. Brolucizumab represents a possible drug switching option in non-responding patients to other anti-VEGF drugs.

Blue light filtering ophthalmic lenses: A systematic review.

Background: Blue blocking (BB) lenses, including spectacles and intraocular lenses, work by attenuating short-wavelength light. BB glasses are being marketed with the aim to reduce eye fatigue symptoms when using digital devices, improve sleep quality and potentially confer protection from retinal phototoxicity. BB intraocular lenses following cataract surgery may be implanted because they are thought to prevent age-related macular degeneration (AMD) progression.Methods: The present study is a systematic review aiming to analyze BB lenses clinical efficacy in preventing blue light-related ocular disorders, including AMD progression, eye fatigue, and their impact on sleep quality. We searched Medline, PubMed, Web of Science and the Cochrane Library until May 2020.Results:Although several studies have been performed investigating BB lenses, clinical efficacy for preventing or attenuating the above-mentioned ocular disorders is often theorical or based on laboratory or animal experiments. Conclusions: To date, there is a lack of consistent evidence for a larger-sclale introduction of BB lenses in the routine clinical practice.

Faricimab: an investigational agent targeting the Tie-2/angiopoietin pathway and VEGF-A for the treatment of retinal diseases.

INTRODUCTION: Intravitreal antivascular endothelial growth factor (VEGF) drugs represent the first-line treatment option for wet age-related macular degeneration (w-AMD) and diabetic macular edema (DME); however, the frequent injection intervals have illuminated to the necessity for new molecules allowing a more prolonged treatment regimen. Faricimab is a promising bispecific drug targeting VEGF-A and the Ang-Tie/pathway. Phase II STAIRWAY and AVENUE Trials showed its clinical efficacy for the treatment of w-AMD, while the phase II BOULEVARD Trial revealed its superiority to monthly ranibizumab in the management of DME with a monthly treatment regimen. The agents are awaiting approval for the treatment of w-AMD and DME. AREAS COVERED: This article presents an overview of w-AMD and diabetic retinopathy and examines the progress of Faricimab through clinical trials. It offers insights on where Faricimab may be placed in the future market of anti-VEGF treatments and discusses the role of Ang/Tie pathway as a potential additive weapon for the treatment of w-AMD, DME, and retinal vein occlusion (RVO). EXPERT OPINION: The possibility of administering faricimab with more prolonged treatment intervals represents an important advantage to decrease the treatment burden and improve patient compliance. Further phase III trials should provide more evidence on clinical efficacy.

Biometric and refractive errors evaluation in patients with neurofibromatosis type 1.

PURPOSE: To analyze biometric changes and prevalence of refractive in patients with neurofibromatosis type 1 (NF1). METHODS: Retrospective, case-controlled study involving patients affected by NF1 and healthy control subjects. Data on biometric measurements such as axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), keratometry (K1 and K2) values, and white-to-white (WTW), obtained by use of optical low-coherence reflectometry on a Lenstar LS 900® (Haag-Streit AG, Switzerland) were collected and analyzed. Cycloplegic refractions were then performed. RESULTS: Overall, 166 eyes of 83 patients diagnosed with NF1 (mean age 21.6 ± 9.8) were enrolled and compared with 178 eyes of age-matched healthy subjects (mean age 22.6 ± 6.6). One hundred sixty-six (22.8%) and 33 of 178 (18.5%) eyes were myopic in NF1 patients and healthy subjects, respectively. The prevalence of hyperopia in the NF1 group was 12 of 166 (7.2%) whereas in the healthy control group was 14 of 178 (8.9%). Twenty-nine of 166 (17.4%) and 34 of 178 (19.1%) eyes presented astigmatism in NF1 and control group, respectively. These differences were not statistically significant (p-values > 0.05). Refractive errors such as myopia, hyperopia, and astigmatism were similar between the two groups. The difference of AL, CCT, ACD, LT, K values, and WTW were no statistically significant between the two groups (p-values > 0.05). CONCLUSION: Refractive errors and ocular biometric parameter seem not to be an addition findings of NF1.

Abicipar pegol: an investigational anti-VEGF agent for the treatment of wet age-related macular degeneration.

INTRODUCTION: Several approaches have been investigated for the management of wet age-related macular degeneration (w-AMD); however, the first-line treatment option for w-AMD currently constitutes anti-VEGF agents. Abicipar pegol is a designed ankyrin repeat protein (DARPin), a novel, promising anti-VEGF agent for the treatment of w-AMD and is reviewed in this article. AREAS COVERED: We discuss the pharmacokinetic, pharmacodynamic, clinical, and tolerability profile revealed by phase II REACH, CYPRESS, and BAMBOO and phase III CEDAR and SEQUOIA Trials. These two latter phase III trials revealed the non-inferiority of abicipar pegol administered with a bimonthly and quarterly regimen when compared with monthly ranibizumab. EXPERT OPINION: Abicipar pegol has been proven to be an emerging, promising anti-VEGF agent in the management of w-AMD. The possibility of adopting a quarterly regimen would allow a decrease in treatment burden and improve patient compliance; however, further larger-scale studies should better characterize abicipar pegol clinical efficacy over longer follow-up periods.

Real-Life Data in the Treatment of Neovascular Age-Related Macular Degeneration: Results from the Imaculaweb Registry Evaluated in a Single Italian Medical Retina Center.

INTRODUCTION: The aim of this study is to assess and compare the long-term clinical efficacy of anti-VEGF drugs using the Imaculaweb registry. METHODS: In this observational study based on the Imaculaweb registry, outcome measures were the number of injections, the change in mean visual acuity (VA) and central macular thickness (CMT), and the time between diagnosis and the first injection. RESULTS: In total, 126 eyes of 109 patients were included in the study. The mean VA was 49.4 ± 21.4, 54.1 ± 22.2, 51.6 ± 24.9, and 48.3 ± 25.7 letters at baseline and at the 1-, 2-, and 3-year follow-ups, respectively. Significant VA increases (p = 0.0002 for the first year and p = 0.045 for the second year) were documented at years 1 and 2 but not at year 3 (p = 0.8). The mean number of injections was 5.2, 2.6, and 2.3 at the 1-, 2-, and 3-year follow-ups, respectively. In the first year, 30% of the patients received at least 7 injections, while only 6.4% received <3 injections. CMT decreased significantly during the overall follow-up period, and intra- and subretinal fluid decreased (p < 0.0001). CONCLUSION: Imaculaweb turned out to be an effective tool to collect and share clinical data as well as to monitor patient outcome.

Endometriosis Classification and The Role of Tumor Necrosis Factor-Alpha Polymorphisms as A Therapeutic Target.

In the recent original research published on International Journal of Fertility and Sterility the association between tumor necrosis factor-alpha (TNF-α) genetic polymorphisms and endometriosis in 150 Iranian patients suffered this disease. The authors notably found a lower frequency of TNF-α -863C/A allele A among the affected patients in comparison with healthy women, although this difference was not significant by adjusting multiple testing. We deem that the authors should specify, if these patients had peritoneal nodules, ovarian endometrioma/deep infiltrating endometriosis (DIE) nodules or combination of them, since it has been hypothesized that these phenotypes may represent three distinct pathogenetic entities of endometriosis.