Transforming the future of ophthalmology: artificial intelligence and robotics' breakthrough role in surgical and medical retina advances: a mini review.

Over the past decade, artificial intelligence (AI) and its subfields, deep learning and machine learning, have become integral parts of ophthalmology, particularly in the field of ophthalmic imaging. A diverse array of algorithms has emerged to facilitate the automated diagnosis of numerous medical and surgical retinal conditions. The development of these algorithms necessitates extensive training using large datasets of retinal images. This approach has demonstrated a promising impact, especially in increasing accuracy of diagnosis for unspecialized clinicians for various diseases and in the area of telemedicine, where access to ophthalmological care is restricted. In parallel, robotic technology has made significant inroads into the medical field, including ophthalmology. The vast majority of research in the field of robotic surgery has been focused on anterior segment and vitreoretinal surgery. These systems offer potential improvements in accuracy and address issues such as hand tremors. However, widespread adoption faces hurdles, including the substantial costs associated with these systems and the steep learning curve for surgeons. These challenges currently constrain the broader implementation of robotic surgical systems in ophthalmology. This mini review discusses the current research and challenges, underscoring the limited yet growing implementation of AI and robotic systems in the field of retinal conditions.

Long-Term results of macular buckle for MTM stage 3-4 With maculoschisis and macular detachment without and With lamellar macular hole.

PURPOSE: To report the long-term anatomical and functional results of macular buckle for Myopic Traction Maculopathy (MTM) in stages 3a, 3b, 4a, and 4b according to the MTM Staging System (MSS). METHODS: Retrospective observational cohort study involving 55 consecutive patients with MTM in stages 3a, 3b, 4a, and 4b who underwent macular buckle (MB). Postoperative outcomes, including optical coherence tomography (OCT) scans to evaluate the MTM stage and its progression, were evaluated 1-month postoperatively (i.e., "intermediate follow-up") and at last follow-up ranging between 6 and 156 months postoperatively (i.e., "final follow-up"). RESULTS: Fifty-five eyes affected by MTM who underwent MB were enrolled. The mean preoperative and postoperative axial length was 31.13 ± 2.14 and 29.73 ± 2.16 mm, respectively (p < 0.01), with a mean axial shift of 1.32 ± 0.77 mm. The mean sample best corrected visual acuity (BCVA) at baseline, intermediate, and final follow-ups was 0.87 ± 0.36, 0.73 ± 0.31, 0.41 ± 0.32 logMar, respectively (p < 0.01). Foveal and retinal anatomical improvements were achieved in 50 (91%) and 53 (96.4%) eyes at intermediate follow-up, respectively. In the final follow-up, 54 (98.2%) and 55 (100%) eyes showed foveal and retinal anatomical improvements, respectively. CONCLUSIONS: MB as a single procedure, when applied to MTM in stages 3a, 3b, 4a, and 4b, leads to significant anatomical and functional improvement. The MTM Staging System allows us to evaluate the best surgical technique and the surgical timing tailored to the different stages to increase the surgery's success and lower the complications of each technique.

Autologous anterior lens capsule flap and serum transplant in managing idiopathic and refractory full-thickness macular holes.

PURPOSE: To report the results of pars plana vitrectomy (PPV) with inner limiting membrane (ILM) peeling alongside phacoemulsification and intraocular lens (IOL) implantation with autologous anterior lens capsule flap (ALCF) and autologous serum transplantation (AST) into full-thickness macular holes (FTMH) and 14% perfluoropropane (C3F8) tamponade for idiopathic and refractory FTMHs. METHODS: Retrospective study involving eleven patients with idiopathic FMTHs and seven with refractory FMTHs after standard surgery with PPV, ILM peeling, and gas tamponade. All eyes underwent a 'combination procedure' of PPV with ILM peeling alongside phacoemulsification and IOL implantation with autologous ALCF and AST into the FTMH and 14% C3F8 tamponade. A face-down position for one week was recommended. RESULTS: The mean preoperative FMTH size was 558.95 ± 186.30 µm. Seven patients aged 64 ± 5 years had a refractory FMTH and eleven patients with a mean age of 63.72 ± 4.97 years had an idiopathic FMTH. The main BCVA improvement six months postoperatively was 0.3 ± 0.29 logMAR. Seventeen macular holes fully closed six months postoperatively, with one FTMH closure failure because of a retinal detachment. CONCLUSIONS: ALCF transplantation alongside AST may help to improve the closure rate and visual outcomes in both idiopathic and refractory FMTHs.

The Role of the Intraoperative Optical Coherence Tomography for Vitreoretinal Surgery in a Real-Life Setting.

BACKGROUND: To descriptively report the advantages and the feasibility of microscope-integrated intraoperative optical coherence tomography (i-OCT) in managing different vitreoretinal diseases in a real-life setting. METHODS: We conducted an observational retrospective study involving 265 eyes that underwent elective retinal surgery and intraoperative OCT between 1 September 2018 and 1 October 2022 at Eyecare Clinic (Brescia, Italy). RESULTS: 52 epiretinal membranes, 30 retinal detachments, 60 high myopic eyes, 30 choroidal transplants, 40 macular holes, and 32 vitreo-proliferative retinopathies underwent vitreoretinal surgery and intraoperative OCT scans. The i-OCT was a useful diagnostic exam for all cases and significantly influenced our surgical management. CONCLUSIONS: i-OCT is a helpful surgical tool in ophthalmic surgery as it provides real-time feedback of tissue anatomy to surgeons, thereby guiding decision-making. Moreover, it provides additional information on the microarchitectural changes after instrument-tissue interactions, further guiding procedures when necessary and possibly reducing unessential surgical maneuvers.

Faricimab: Transforming the Future of Macular Diseases Treatment - A Comprehensive Review of Clinical Studies.

Degenerative eye conditions such as age-related macular degeneration (AMD), diabetic retinopathy, and retinal vein occlusion are major contributors to significant vision loss in developed nations. The primary therapeutic approach for managing complications linked to these diseases involves the intravitreal delivery of anti-vascular endothelial growth factor (VEGF) treatments. Faricimab is a novel, humanised, bispecific antibody that simultaneously binds all VEGF-A isoforms and Angiopoietin-2, which has been approved by regulatory agencies, such as the US Food and Drug Administration (FDA), the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA), for the treatment of neovascular AMD and diabetic macular oedema (DMO). Intravitreal faricimab holds the promise of reducing the treatment burden for patients with these conditions by achieving comparable or superior therapeutic outcomes with fewer clinic visits. The scope of faricimab's application includes addressing complex macular conditions such as DMO. This review intends to elucidate the distinctive pharmacological characteristics of faricimab and provide an overview of the key clinical trials and real-world studies that assess its effectiveness and safety in treating degenerative macular diseases.

Intravitreal Fluocinolone Acetonide Implant (ILUVIEN®) for the Treatment of Retinal Conditions. A Review of Clinical Studies.

Fluocinolone acetonide (FAc) intravitreal implant (Iluvien®) is a corticosteroid implant indicated for the treatment of diabetic macular oedema (DMO) in patients who have previously received conventional treatment without good response, non-infectious posterior uveitis, and as an off-label treatment of the macular oedema secondary to retinal vein occlusion. FAc is a non-biodegradable 0.19 mg intravitreal implant which is designed to release FAc over 3 years at a rate of approximately 0.2 mcg per day. The aim of this review is to describe the special pharmacological properties of Iluvien and display the outcomes of the most important clinical trials and real-world studies regarding its efficacy and safety for the management of the above retinal disorders.

Sympathetic Ophthalmia after Vitreoretinal Surgery without Antecedent History of Trauma: A Systematic Review and Meta-Analysis.

BACKGROUND: To evaluate the morbidity frequency measures in terms of the cumulative incidence of sympathetic ophthalmia (SO) triggered by single or multiple vitreoretinal (VR) surgery procedures in eyes without an antecedent history of trauma and previous ocular surgery, except for previous or concomitant uneventful lens extraction, and to further investigate the relationship between VR surgery and SO. METHODS: A literature search was conducted using PubMed, Embase, and Scopus from inception until 11 November 2022. The Joanna Briggs Institute (JBI) critical appraisal checklist for the case series and the Newcastle-Ottawa Scale were used to assess the risk of bias. The research was registered with the PROSPERO database (identifier, CRD42023397792). Meta-analyses were conducted using the measurement of risk and a 95% confidence interval (CI) for each study. RESULTS: A random-effect meta-analysis demonstrated that the pooled cumulative incidence of SO triggered by single or multiple VR surgery procedures in eyes without an antecedent history of trauma and previous ocular surgery, except for previous or concomitant uneventful lens extraction among patients who developed SO regardless of the main trigger, was equal to 0.14 with a CI between 0.08 and 0.21 (I2 = 78.25, z: 7.24, p < 0.01). The pooled cumulative incidence of SO triggered by single or multiple VR surgery procedures in eyes without an antecedent history of trauma and previous ocular surgery, except for previous or concomitant uneventful lens extraction among patients who underwent VR surgery, was equal to 0.03 for every 100 people, with a confidence interval (CI) between 0.02% and 0.004% (I2 = 27.77, z: 9.11, p = 0.25). CONCLUSIONS: Despite postsurgical SO being a rare entity, it is a sight-threatening disease. VR surgery should be viewed as a possible inciting event for SO and considered when counseling patients undergoing VR surgery.

Postoperative complications after successful primary rhegmatogenous retinal detachment repair.

BACKGROUND: To evaluate the incidence and risk factors for cystoid macular edema (CME) and epiretinal membrane (ERM) development after surgery for primary rhegmatogenous retinal detachment (RRD). METHODS: Retrospective observational cohort study involving 62 consecutive patients with primary RRD who underwent RRD repair with either scleral buckling (SB) or pars plana vitrectomy (PPV). SB was used in young phakic patients without posterior vitreous detachment (PVD), high myopic patients, and RRD associated with either anterior or inferior retinal tears. PPV was preferred over SB in pseudophakic patients or those with media opacity and posterior breaks that precluded the SB approach. After surgery, the macular changes, including CME and ERM development, were evaluated 3 and 6 months postoperatively. Phacoemulsification and intraocular lens (IOL) implantation were performed in phakic patients where media opacity or lens bulging did not allow the surgeon to perform surgical maneuvers. The inner limiting membrane (ILM) peeling was randomly performed in the macula-off and the macula-on RRD "pending foveal detachment" subgroup. RESULTS: Sixty-two eyes affected by RRD who underwent SB or PPV were enrolled. CME occurred in 33.3% of the PPV group regardless of the ERM formation. No CME cases were found in the SB group. Macula-off RRD increased the risk of CME by odds ratio (OR) = 4.3 times compared to macula-on RRD regardless of the surgical procedure (p = 0.04). Macula-off status increased the risk of CME of OR = 1.73 times compared to macula-on in the PPV subgroup (p = 0.4). Combined cataract surgery and PPV increased the risk of CME by OR = 3.3 times (p = 0.16) compared to PPV alone, and ILM peeling increased the risk of postoperative CME by OR = 1.8 times (p = 0.37). ERM occurred in 28% of patients who did not undergo ILM peeling, and 29.42% of those who underwent ILM peeling developed ERM (p = 0.6). CONCLUSIONS: The risk of postoperative CME was higher in patients with macula-off than in macula-on RRD and in those with macula-off RRD who underwent PPV. The SB would be advisable in patients with RRD sparing the macula. Furthermore, despite having several advantages, the combined phacoemulsification plus IOL implantation and PPV highly increased the risk of postoperative CME.

Three-Dimensional Heads-Up vs. Standard Operating Microscope for Cataract Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: The surgical time duration, the postoperative best-corrected visual acuity (BCVA), and the incidence rate of intraoperative complications, alongside the vision and posturing parameters, were estimated by systematic review and meta-analysis to compare the three-dimensional (3D) heads-up visualization system (HUVS) and standard operating microscope (SOM) in cataract surgery. METHODS: A literature search was conducted using PubMed, Embase, and Scopus on 26 June 2022. The weighted mean difference (WMD) was used to present postoperative BCVA and the mean surgical time duration, whereas the risk ratio (RR) was used to present the incidence rate of intraoperative complications. Publication bias was evaluated with Egger's test. The Cochrane Collaboration's Tool for randomized clinical trials, the methodological index for non-randomized, and the Newcastle-Ottawa Scale were used to assess the risk of bias. The research has been registered with the PROSPERO database (identifier, CRD42022339186). RESULTS: In the meta-analysis of five studies with 1021 participants, the pooled weighted mean difference (WMD) of the postoperative BCVA showed no significant difference between patients who underwent HUVS versus SOM cataract surgery (WMD = -0.01, 95% confidence interval (CI): -0.01 -0.02). In the meta-analysis of nine studies with 5505 participants, the pooled WMD of mean surgical time duration revealed no significant difference between patients who underwent HUVS versus SOM cataract surgery (WMD = 0.17, 95% CI: -0.43-0.76). In the meta-analysis of nine studies with 8609 participants, the pooled risk RR associated with intraoperative complications was 1.00 (95% CI, 1.00-1.01). CONCLUSIONS: 3D HUVS and SOM provide comparable surgical time duration, postoperative BCVA, and incidence rate of intraoperative complications.

The Role of Widefield and Ultra Widefield Optical Coherence Tomography in the Diagnosis and Management of Vitreoretinal Diseases.

BACKGROUND: This study reports on the advantages of wide-field (WF)- and ultra-widefield (UWF)- optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) in managing different vitreoretinal diseases in a real-life setting using the new WF-Swept Source (SS)-OCT Xephilio S1 (Canon, Tokyo, Japan). METHODS: We conducted an observational retrospective case series study involving 1472 eyes that underwent retinal scans with Canon Xephilio® OCT-S1 between 1 March 2021 and 1 December 2021 at Eyecare Clinic (Brescia, Italy). All patients underwent routine ophthalmologic examinations along with WF and UWF color fundus retinography with Clarus 500™ (Carl Zeiss Meditec, Inc., Dublin, CA, USA) and Xephilio® OCT-S1. WF SS-OCT, UWF-OCT, WF-OCTA, and UWF-OCTA were taken by using Xephilio® OCT-S1. RESULTS: We analyzed 122 peripheral retinal lesions, 144 retinal detachment, 329 high myopic eyes, 37 pediatric cases, 60 vascular retinopathies, 15 choroidal lesions, and 90 eyes as follow-up post vitreoretinal surgery. The OCT-S1 was the only reliable and diagnostic exam for peripheral lesions, pediatric and high myopic cases, and significantly influenced the management in 10% of cases and the postoperative follow-up. CONCLUSIONS: WF and UWF OCT and OCTA imaging may help in the management of several vitreoretinal diseases, becoming an indispensable tool for the high-quality management of patients.

COMPARISON OF PAIN EXPERIENCE IN PATIENTS UNDERGOING SUB-TENON'S ANESTHESIA VERSUS PERIBULBAR ANESTHESIA DURING ELECTIVE VITREORETINAL SURGERY.

PURPOSE: To assess and compare the patients' discomfort and pain experienced during anesthesia, pars plana vitrectomy, and 24 hours postoperatively after sub-Tenon's injection (STI) versus peribulbar block (PB) in elective vitreoretinal surgery. METHODS: Retrospective study involving 80 patients who underwent elective vitreoretinal surgery receiving either PB (Group 1, n = 40) or STI (Group 2, n= 40) between January 2021 and March 2022. Patients' pain experienced during the procedure and 24 hours postoperatively were assessed using a pain scale and a two-section questionnaire. One hour postoperatively, patients were asked to rate the level of pain they felt during the entire procedure by pointing at a 0 to 100 Visual Analog Scale. Subsequently, patients answered a two-section questionnaire regarding pain and discomfort felt 24 hours postoperatively. RESULTS: According to Visual Analog Scale measurements, patients experienced significantly more pain during PB than during STI 1 hour after surgery. Patients undergoing PB experienced more pain than those who underwent STI, experiencing burning and discharge feeling. Patients undergoing STI had a lower pain level score 24 hours postoperatively despite similar discomfort. CONCLUSION: Sub-Tenon's injection has a lower pain score than PB during the procedure and 24 hours postoperatively, representing a valuable procedure to deliver analgesia in vitreoretinal surgery.

The Impact of Steep Trendelenburg Position on Intraocular Pressure.

Intraocular pressure occurring during the Trendelenburg position may be a risk for postoperative visual loss and other ocular complications. Intraocular pressure (IOP) higher than 21 mmHg poses a risk for ocular impairment causing several conditions such as glaucoma, detached retina, and postoperative vision loss. Many factors might play a role in IOP increase, like peak expiratory pressure (PIP), mean arterial blood pressure (MAP), end-tidal CO2 (ETCO2) and surgical duration and some others (anaesthetic and neuromuscular blockade depth) contribute by reducing IOP during procedures requiring both pneumoperitoneum and steep Trendelenburg position (25-45° head-down tilt). Despite transient visual field loss after surgery, no signs of ischemia or changes to the retinal nerve fibre layer (RNFL) have been shown after surgery. Over the years, several studies have been conducted to control and prevent IOPs intraoperative increase. Multiple strategies have been proposed by different authors over the years to reduce IOP during laparoscopic procedures, especially those involving steep Trendelenburg positions such as robot-assisted laparoscopic prostatectomy (RALP), and abdominal and pelvic procedures. These strategies included both positional and pharmacological strategies.

Identification of biomarkers in COPD by metabolomics of exhaled breath condensate and serum/plasma.

Chronic obstructive pulmonary disease (COPD) is the third cause of death worldwide, presenting poor long-term outcomes and chronic disability. COPD is a condition with a wide spectrum of clinical presentations because its pathophysiological determinants relate to tobacco smoke, genetic factors, alteration of several metabolic pathways, and oxidative stress. Consequently, patients present different phenotypes even with comparable degrees of airflow limitation. Because of the increasing social and economic costs of COPD, a growing attention is currently paid to "omics" techniques for more personalized treatments and patient-tailored rehabilitation programs. In this regard, the systematic investigation of the metabolome (i.e., the whole set of endogenous molecules) in biomatrices, namely metabolomics, has become indispensable for phenotyping respiratory diseases. The metabolomic profiling of biological samples contains the small molecules produced during biological processes and their identification and quantification help in the diagnosis, comprehension of disease outcome and treatment response. Exhaled breath condensate (EBC), plasma and serum are biofluids readily available, with negligible invasiveness, and, therefore, suitable for metabolomics investigations. In this paper, we describe the latest advances on metabolomic profiling of EBC, plasma and serum in COPD patients.

Factors predicting normal visual acuity following anatomically successful macular hole surgery.

PURPOSE: To assess the incidence of normal vision following anatomically successful macular hole surgery and associated clinical variables. METHODS: Multicentre, retrospective chart review. Preoperative, intraoperative and postoperative clinical data were extracted from electronic medical records from seven European vitreoretinal units. Inclusion criteria were as follows: eyes undergoing primary vitrectomy for idiopathic full-thickness macular hole from January 2015 to January 2018; postoperative macular hole closure confirmed by spectral domain optical coherence tomography (OCT); preoperative pseudophakia or phakic eyes receiving combined cataract surgery; one-year follow-up. The primary outcome was 'normal vision' defined as a final best-corrected visual acuity (BCVA) ≥ 20/25. Univariate, multivariate and decision-tree analyses were conducted to evaluate the clinical variables associated with 'normal vision'. Odds ratios (OR) and confidence intervals (CIs) were calculated. RESULTS: Of 327 eligible cases, 91 (27.8%) achieved 'normal vision' at 1 year. Multivariate analysis identified variables significantly associated with 'normal vision': shorter symptom duration (odds ratio [OR]=1.05; 95% confidence interval [CI]:1.02-1.09; p = 0.002), smaller preoperative OCT minimum linear diameter (OR per 100-micron increase = 1.65; 95%CI:1.31-2.08; p < 0.001) and better mean preoperative BCVA (OR = 15.13; 95%CI: 3.59-63.65; p < 0.001). The decision-tree analysis found that the most significant variable associated with 'normal vision' was symptom duration. 'Normal vision' was achieved in 70.6% of eyes operated within one week from symptom onset and in 45% of eyes with symptom duration between 1 and 3 weeks. CONCLUSIONS: These findings suggested urgent surgery is justified for small macular holes of short duration.

Central retinal vein occlusion associated with high blood levels of lipoprotein (a).: Is lipoprotein (a) a reliable marker for identification of predisposed individuals?

To report a case of central retinal vein occlusion (CRVO) associated with abnormal elevation of Lipoprotein (a) [Lp(a)] plasma levels, without local or systemic risk factors. A 74-year-old man was referred to our department for cataract surgery in his left eye, and his anamnesis was negative for systemic diseases. Two months later, the patient presented with sudden visual loss in his operated eye, and comprehensive ophthalmic examination was performed, including Fluorescein Angiography (FA) and Optical Coherent Tomography (OCT). Serum concentrations of anticardiolipin and antiphospholipids antibodies, homocysteine and Lp(a) were measured. Ophthalmoscopy showed the classic features of acute CRVO, FA and OCT confirmed the initial diagnosis. Blood tests were negative for hyperhomocysteinemia, anticardiolipin and antiphospholipids antibodies, and an abnormal Lp(a) plasma concentration of 1.7 g/L was found. The patient was sent to the internist for further investigation and treatment. Lp(a) can be an useful marker for early identification of predisposed individuals to CRVO and may be involved in its pathogenesis, presumably through its pro-atherogenic and antifibrinolytic action.

Association between metalloproteinases 2 and 9 activity and ERK1/2 phosphorylation status in head and neck cancers: an ex vivo study.

Advances in clinical treatment of head and neck squamous cell carcinoma (HNSCC) are hampered by its high infiltrative potential leading to distal metastasis. Since their ability to degrade the basal lamina and extracellular matrix, matrix metalloproteinases (MMP) have a pivotal role in tumor invasion. The overexpression and the aberrant activity of MMPs especially of MMP2 and MMP9, during HNSCC development and progression have been reported. However, up to now little is known about the mechanism of their regulation in HNSCC. It has been demonstrated that MMP2/9 expression is negative regulated by extracellular signal regulated kinase 1 and 2 (ERK1/2) in HNSCC cell lines. ERKs are protein kinases belonging to the mitogen-activated protein kinases family, and they are involved in the regulation of different cellular aspects, from apoptosis to cell proliferation and differentiation. In the present study we evaluated MMP2 and MMP9 activity by gelatine zymography in 16 tissue samples of HNSCC and their paired normal mucosa from patients undergoing surgical treatment. Moreover, ERK1/2 activation was analyzed by immunoblotting. A statistically significant decrease in the levels of activated ERK2 in cancer specimens in comparison with paired normal tissues was observed, whereas a significant increase in the activity of MMP2 was found in cancer specimens. However, the statistical analysis failed to demonstrate a correlation between the increase in MMP2 activity and the reduction of ERK1/2 activation levels. The results obtained, therefore, rule out, for the first time in an ex vivo study, the existence of a negative correlation between ERK1/2 activation and MMP2 activity.

Intravitreal triamcinolone for macular edema in Lyme disease.

BACKGROUND: To describe the outcome in a patient with macular edema caused by Lyme disease treated with injection of 4 mg intravitreal triamcinolone. METHODS: The patient, 2 years after systemic Lyme disease treated with doxycycline for 4 weeks, developed macular edema with serous retinal detachment in one eye (visual acuity: 0.6). After unsuccessful therapy with intravenous ceftriaxone, indomethacin and acetazolamide, 4 mg intravitreal triamcinolone (IVTA) was injected via the pars plana. RESULTS: Visual acuity improved to 1.0 and macular thickness recovered over 1 month. No changes were found in intraocular pressure. No recurrence of macular edema was seen after 2 years. CONCLUSIONS: IVTA can restore visual acuity and reduce macular thickness in macular edema caused by Lyme disease. However, since borreliosis is a systemic disease, previous systemic antibiotic treatment is recommended.