Autonomous artificial intelligence versus teleophthalmology for diabetic retinopathy.

Purpose: To assess the role of artificial intelligence (AI) based automated software for detection of Diabetic Retinopathy (DR) compared with the evaluation of digital retinography by two double masked retina specialists. Methods: Two-hundred one patients (mean age 65 ± 13 years) with type 1 diabetes mellitus or type 2 diabetes mellitus were included. All patients were undergoing a retinography and spectral domain optical coherence tomography (SD-OCT, DRI 3D OCT-2000, Topcon) of the macula. The retinal photographs were graded using two validated AI DR screening software (Eye Art TM and IDx-DR) designed to identify more than mild DR. Results: Retinal images of 201 patients were graded. DR (more than mild DR) was detected by the ophthalmologists in 38 (18.9%) patients and by the AI-algorithms in 36 patients (with 30 eyes diagnosed by both algorithms). Ungradable patients by the AI software were 13 (6.5%) and 16 (8%) for the Eye Art and IDx-DR, respectively. Both AI software strategies showed a high sensitivity and specificity for detecting any more than mild DR without showing any statistically significant difference between them. Conclusions: The comparison between the diagnosis provided by artificial intelligence based automated software and the reference clinical diagnosis showed that they can work at a level of sensitivity that is similar to that achieved by experts.

Predictors of 24-month onset of macular fibrosis in type 3 macular neovascularisation.

AIMS: To explore prognostic multimarker models for progression to macular fibrosis (MF) over 24 months specific to type 3 macular neovascularisation (T3 MNV). METHODS: This retrospective, exploratory, single-centre, cohort study comprised 65 eyes of 43 Caucasian patients with treatment naive T3 MNV, all with a 24-month follow-up post anti-VEGF therapy using a strict pro-re-nata (PRN) regimen. Data on demographic features, clinical findings, frequency of intravitreal treatments and optical coherence tomography biomarkers were collected at baseline and after 12 and 24 months of follow-up. Logistic regression models (LRM) and receiver-operating curve (C-index) analyses were performed to evaluate the prognostic ability of the studied biomarkers in discriminating between MF affected and unaffected patients. RESULTS: At final follow-up, MF was present in 46.2% of eyes. Subretinal hyper-reflective material (SHRM) and subretinal pigment epithelium multilaminar hyper-reflectivity (multilaminae) emerged as significant predictors for MF, with adjusted odds ratios (OR) of 18.0 (95% CL 13.4 to 24.1) and 11.8 (95% CL 8.66 to 16.0), respectively. Additionally, the presence of multifocal lesions (OR 0.04, 95% CL 0.01 to 0.30) appeared to decrease the likelihood of MF. C-indexes for the selected LRMs ranged between 0.92 and 0.88, indicating a comparably high discriminant ability. Despite consistent treatment schedules between the two groups (MF: median intravitreal treatment (IVT) number=10.5, IQR=7; non-MF: median IVT=10, IQR=6), a decline in best-corrected visual acuity was noted in the group with MF onset over the 24-month follow-up (-13.0 ETDRS letters; 95% CL -22.1 to -3.9; p=0.006). CONCLUSION: Our study identifies SHRM and multilaminae as relevant predictors of 24-month onset of MF in patients with T3 MNV. These findings enrich our understanding of the development of MF in T3 MNV and can guide improved risk prognostication. Future research should consider larger samples and prospective designs to validate these predictors.

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.

Peripheral and ocular microvascular alterations in systemic sclerosis: observations from capillaroscopic assessments, perfusion peripheral analysis, and optical coherence tomography angiography.

To investigate the correlations between finger microvascular morphology and function in patients with systemic sclerosis (SSc) and the status of ocular microcirculation, as detected by nailfold videocapillaroscopy (NVC), laser speckle contrast analysis (LASCA), and optical coherence tomography angiography (OCTA). The enrollment included 32 SSc patients, classified according to the 2013 ACR/EULAR criteria, and 27 sex- and age-matched healthy controls. The participants underwent comprehensive rheumatological and ophthalmological examinations, as well as NVC, LASCA, and OCTA analysis on the same day at a single center from March to October 2022. SSc patients receiving intravenous prostanoids cycles were assessed at least 1 month after infusion. Statistical analysis was conducted using Stata® 15.1. Significant direct correlations were observed between the mean capillary number (at NVC) and the mean perfusion of fingers (at LASCA) with the retinal and choroidal perfusion (at OCTA) (all p < 0.05). In addition, a significantly reduced retinal and choroidal perfusion was detected in SSc patients vs controls (all p < 0.05). Interestingly, diffuse cutaneous SSc (dcSSc) patients exhibited a lower choroidal perfusion (p = 0.03) but an increased choroidal thickness (CT) than limited cutaneous SSc patients (p < 0.001). CT was increased also in patients with positive Scl70 antibodies and with a history of digital ulcers directly correlating with disease duration (r = 0.67, p = 0.001). Finally, the combination of LASCA and OCTA parameters showed a significant discrimination capacity between SSc patients and controls, with an area under the curve of 0.80 [95% CI (0.74, 0.87)]. Peripheral microvascular damage is correlated with impaired ocular microcirculation in SSc. The increased choroidal thickness observed in dcSSc may be related to local sub-endothelial extracellular matrix deposition. The combined analysis of choroidal and fingertip perfusion offers preliminary insights that may complement traditional diagnostic methods for SSc.

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.

Clinical Outcomes of Topical 0.1% Ciclosporin Cationic Emulsion Used on Label in Children with Vernal Keratoconjunctivitis.

INTRODUCTION: The purpose of this short article is to report the clinical outcomes of topical 0.1% ciclosporin cationic emulsion (CsA-CE) used on label in children with vernal keratoconjunctivitis (VKC). METHODS: In this prospective, non-comparative, observational study children affected by active severe VKC were treated for at least 12 months with topical 0.1% CsA-CE. The drug was instilled in both eyes 4 times daily. Data collected from medical charts for the baseline visit (T0) and 1-year follow-up visit (T1) included symptomatic score (0-15), clinical score (0-15), side effects, rescue therapy (need and total number of courses with 0.1% dexamethasone 4 times daily for 5 days), ocular complications and tolerability (visual analog scale [0-100]). RESULTS: Data from 25 children (20 boys, 5 girls; mean [± standard deviation] age 8.40 ± 2.54 years) were included in the study. Of the 25 patients, 23 (92%) used 0.1% CsA-CE eye drops as per label recommendations, including four patients who had prematurely stopped using topical galenic CsA due to side effects. Symptomatic and clinical scores decreased significantly after treatment, with the mean symptomatic score decreasing from 9.76 ± 1.27 at T0 to 3.80 ± 1.08 at T1, and the mean clinical score decreasing from 9.20 ± 1.32 at T0 to 3.44 ± 1.00 at T1; both P < 0.0001). Five patients (20%) required at least one course of rescue medication (mean 3.4 ± 4.8 courses/year). No patients experienced ocular complications during the study, and treatment tolerability was very high (mean score 89.40 ± 5.46). CONCLUSION: Our findings confirm that topical CsA-CE is an effective on-label option for children with VKC in the real-life setting. In our pediatric patient population, CsA-CE provided good clinical outcomes with a limited need for rescue medication, and it was well tolerated by almost all patients, including those who were intolerant to galenic formulations.

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.

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.

Vigorous Physical Activity as a Risk Factor for Central Serous Chorioretinopathy.

PURPOSE: To evaluate whether frequent vigorous physical activity (PA) is significantly associated with active central serous chorioretinopathy (CSCR) and may represent a risk factor for CSCR. DESIGN: Case-control study. METHODS: This was a multicenter study. The patient population comprised consecutive patients with active CSCR and a comparable control group of healthy participants. Both groups were interrogated about their PA using a shortened version of the International Physical Activity Questionnaire. The Ainsworth Compendium of Physical Activities was taken as a reference for the activities requiring vigorous effort and to quantify the energy expended, expressed in metabolic equivalent of task (MET). As a main outcome measure, a moderate/high practice of vigorous PA was opposed to an absent/low practice of vigorous PA in the 2 groups. RESULTS: A total of 105 patients with CSCR and 105 healthy controls were included in the study. Moderate/high vigorous PA was observed in 63.5% of the patients with CSCR and in 26% of the controls (P = .0001). The MET values of vigorous PA were 2173.2 ± 2081.5 in the CSCR group and 1216.3 ± 524 in the control group (P = .029). The potential risk of disease associated with moderate/high vigorous PA was 5.58 (odds ratio; 95% confidence interval 3.01-10.69, P = .0001). CONCLUSIONS: This study demonstrates a significant association of vigorous PA with CSCR, indicating an increased probability of disease by 5.58 times. Frequent and intense PA, with the hypertensive episodes that it entails, can break the precarious hemodynamic balance in the choroid of individuals predisposed to CSCR, thereby favoring choroidal vascular decompensation and active disease.

PERSEUS-IT 24-month analysis: a prospective observational study to assess the effectiveness of intravitreal aflibercept in routine clinical practice in Italy in patients with neovascular age-related macular degeneration.

PURPOSE: PERSEUS-IT (NCT02289924) was a prospective, observational, 2-year study evaluating the effectiveness and treatment patterns of intravitreal aflibercept (IVT-AFL) in patients with neovascular age-related macular degeneration (nAMD) in routine clinical practice in Italy. METHODS: Treatment-naïve patients with nAMD receiving IVT-AFL per routine clinical practice were enrolled. The primary endpoint was mean change in visual acuity (VA; decimals) from baseline to month (M) 12 and M24. Outcomes were evaluated for the overall study population and independently for the 2 treatment cohorts: regular (3 initial monthly doses, ≥ 7 injections by M12, and ≥ 4 injections between M12 and M24) and irregular (any other pattern). RESULTS: Of 813 patients enrolled, 709 were included in the full analysis set (FAS); VA assessments were available for 342 patients at M12 (FAS1Y, 140 regular and 202 irregular) and 233 patients at M24 (FAS2Y, 37 regular and 196 irregular). In the overall FAS, the mean ± SD change in VA from baseline to M12 and M24 was + 0.09 ± 0.24 and + 0.02 ± 0.25 decimals, and there was a statistically significant difference between the regular and irregular cohorts in both FAS1Y (p = 0.0034) and FAS2Y (p = 0.0222). Ocular treatment-emergent adverse events were reported in 4.1% (n = 33/810 [safety set]) of patients. CONCLUSION: In PERSEUS-IT, clinically relevant functional and anatomic improvements were observed within the first 12 months of IVT-AFL treatment in routine clinical practice in Italy in patients with treatment-naïve nAMD. These gains were generally maintained across the 2-year study. The safety profile of IVT-AFL was consistent with prior studies. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT02289924. DATE OF REGISTRATION: November 13, 2014.

The multifaceted presentation of syphilitic chorioretinitis examined by multimodal imaging: A case series.

Ocular syphilis is also known as the 'great masquerader' for the wide variety of clinical features associated with this infection. Although chorioretinitis represents the most frequent manifestation in the posterior pole, other clinical entities can be described, including retinal vasculitis, optic disc disorders, necrotizing vasculitis and acute syphilitic posterior placoid chorioretinopathy (ASPPC).This latter is an infrequent ocular manifestation of syphilis, whose pathophysiology remains still unknown; however, multimodal imaging, including optical coherence tomography angiography (OCTA), has enabled us to better describe its pathophysiology and clinical course.In this study we report a case series of 3 different patients with syphilis-related chorioretinopathies; in this regard, the role of multimodal imaging has emerged has an extremely useful approach in order to better understand the pathophysiology of syphilitic chorioretinopathies. This could help clinicians (both ophthalmologist and infectious disease specialists) to early treat and prevent the severe ocular complications related to this fearsome disease.

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.

Intravitreal Corticosteroid Implantation in Diabetic Macular Edema: Updated European Consensus Guidance on Monitoring and Managing Intraocular Pressure.

Intravitreal therapy for diabetic macular edema can, in susceptible patients, increase intraocular pressure (IOP). As uncontrolled IOP can potentially be sight threatening, monitoring is an essential component of patient management. It can be challenging for retina specialists to ensure that monitoring is rigorous enough to detect and resolve any potential problems at the earliest opportunity without it also being overburdensome for patients who have the lowest risk of developing an IOP rise. We have developed dynamic algorithms that: (1) tailor the frequency and extent of monitoring according to individual susceptibility and current IOP and (2) assist retina specialists in deciding when they should consider a referral to a glaucoma specialist. One algorithm is for patients with a relatively low susceptibility to developing an IOP rise (those whose baseline IOP is < 22 mmHg and who do not have a history of IOP events). Depending on their first post-implantation IOP check, the algorithm classifies them as: low risk if IOP remains < 22 mmHg; medium risk if IOP is 22-25 mmHg and any rise from baseline is < 10 mmHg; or high risk if IOP is > 25 mmHg or any rise from baseline is ≥ 10 mmHg. Thereafter, the algorithm guides on the frequency and extent of monitoring required in each of these groups and, if IOP rises or falls during treatment, patients may move up or down the risk groups accordingly. A different algorithm is provided for patients who are more susceptible to developing an IOP rise (those with a baseline IOP of ≥ 22 mmHg or a prior history of an IOP event). These patients need monitoring more closely so this algorithm has only medium- or high-risk classifications. These algorithms update the previous monitoring guidance by Goñi et al. (Goñi et al. in Ophthalmol Ther 5:47-61, 2016).

Some people with diabetes have macular edema, which is a swelling of the central part of the retina (the tissue that lines the back of the eye). This swelling can threaten eyesight if untreated.Injecting a drug such as a corticosteroid into the eye can help treat the condition. Sometimes this has a side effect of increasing intraocular pressure (pressure within the eye). A small or short-lived rise in eye pressure should be no cause for concern, but it is very important to ensure the pressure is not too high for too long­because this could lead to the loss of eyesight. To prevent this happening, an eye doctor needs to check the eye pressure regularly.Some people are more susceptible to this problem­for example, people who have had any problems related to eye pressure in the past or people whose eyes already have a higher than normal pressure even before treatment. People who are most susceptible may need more types of checks and more frequent checks to ensure that any problems are found and treated quickly.We have developed flowcharts that help eye doctors decide which checks are needed and how often based on what the doctor knows about the person's eye before treatment and what they see at each check-up after treatment. They help doctors make sure that everyone has check-ups at the right time and they help doctors spot any problems early so that they can be resolved before long-lasting damage can occur.

Concerns on ranibizumab and zoledronic acid safety for experimentally treating women with endometriosis.

Correspondence to the original research entitled "Effects of ranibizumab and zoledronic acid on endometriosis in a rat model" published by Ozdemir et al.

Bilateral choroidal detachment and myopic shift after acetazolamide intake for laser capsulotomy.

INTRODUCTION: To report a case of bilateral choroidal effusion after laser capsulotomy. CASE DESCRIPTION: A healthy 85 years old white woman was referred to our hospital with a diagnosis of posterior capsule opacification in the left eye. The patient was treated with laser capsulotomy and oral acetazolamide was administered after the procedure. The day after, the patient visited the emergency room complaining bilateral blurred vision. A myopic shift and peripheral choroidal detachment was noted in both eyes. Discontinuation of acetazolamide and treatment with topical steroid and cyclopentolate resulted in a significant improvement in visual acuity and the complete resolution of the choroidal detachment in 1 week. CONCLUSION: To the best of our knowledge, this is the first reported case of choroidal detachment and acute transient myopia following the administration of oral acetazolamide after laser capsulotomy.

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.

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.