Sex-related differences in serum biomarker levels predict the activity and efficacy of immune checkpoint inhibitors in advanced melanoma and non-small cell lung cancer patients.

BACKGROUND: Immune Checkpoint Inhibitors (ICIs) lead to durable response and a significant increase in long-term survival in patients with advanced malignant melanoma (MM) and Non-Small Cell Lung Cancer (NSCLC). The identification of serum cytokines that can predict their activity and efficacy, and their sex interaction, could improve treatment personalization. METHODS: In this prospective study, we enrolled immunotherapy-naïve patients affected by advanced MM and NSCLC treated with ICIs. The primary endpoint was to dissect the potential sex correlations between serum cytokines (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, GM-CSF, MCP-1, TNF-ɑ, IP-10, VEGF, sPD-L1) and the objective response rate (ORR). Secondly, we analyzed biomarker changes during treatment related to ORR, disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Blood samples, collected at baseline and during treatment until disease progression (PD) or up to 2 years, were analyzed using Luminex xMAP or ELLA technologies. RESULTS: Serum samples from 161 patients (98 males/63 females; 92 MM/69 NSCLC) were analyzed for treatment response. At baseline, IL-6 was significantly lower in females (F) versus males (M); lower levels of IL-4 in F and of IL-6 in both sexes significantly correlated with a better ORR, while higher IL-4 and TNF-ɑ values were predictive of a lower ORR in F versus M. One hundred and sixty-five patients were evaluable for survival analysis: at multiple Cox regression, an increased risk of PD was observed in F with higher baseline values of IL-4, sPD-L1 and IL-10, while higher IL-6 was a negative predictor in males. In males, higher levels of GM-CSF predict a longer survival, whereas higher IL-1ß predicts a shorter survival. Regardless of sex, high baseline IL-8 values were associated with an increased risk of both PD and death, and high IL-6 levels only with shorter OS. CONCLUSIONS: Serum IL-1ß, IL-4, IL-6, IL-10, GM-CSF, TNF-ɑ, and sPD-L1 had a significant sex-related predictive impact on ORR, PFS and OS in melanoma and NSCLC patients treated with ICIs. These results will potentially pave the way for new ICI combinations, designed according to baseline and early changes of these cytokines and stratified by sex.

Fatigue after spontaneous intracerebral haemorrhage: prevalence and associated factors.

BACKGROUND: Fatigue is a major complaint in stroke survivors, but data focusing on intracerebral haemorrhage (ICH) survivors are scarce. In a cohort of spontaneous ICH survivors, we assessed the long-term prevalence of fatigue and its associated factors. METHODS: We included consecutive 1-year ICH survivors from the prospective, observational, single-centre Prognosis of Intracerebral Haemorrhage (PITCH) study. We evaluated fatigue (defined as a score ≥ 4 in Chalder Fatigue Scale); the severity of neurological, depressive, and anxiety symptoms; and functional disability 1, 3, and 6 years after ICH. We performed univariable and multivariable models to evaluate clinical factors and brain magnetic resonance imaging (MRI) small vessel disease (SVD) markers associated with fatigue. RESULTS: Of 255 1-year ICH survivors, 153 (60%) underwent fatigue screening and were included in this study. Seventy-eight patients (51%) reported fatigue at 1-year, 56/110 (51%) at 3-year, and 27/67 (40%) at 6-year follow-up. Patients with fatigue exhibited more severe concomitant depressive/anxiety symptoms, but the severity of depressive symptoms was the only clinical factor significantly associated with 1-year fatigue in multivariable analysis (adjusted odds ratio 1.4 for one-point increase; 95% confidence interval 1.2-1.6). Patients with severe cortical atrophy at baseline had increased risk of fatigue at 1-year follow-up compared to patients with mild/no cortical atrophy (adjusted odds ratio 2.5; 95% confidence interval 1.1-5.8). CONCLUSIONS: Fatigue after ICH is frequent and long-lasting, and it is associated with cortical atrophy (but not with other MRI markers of cerebral SVD). The link between fatigue and depressive symptoms may represent a potential therapeutic target.

First Prospective Multicenter Italian Study on the Impact of the 21-Gene Recurrence Score in Adjuvant Clinical Decisions for Patients with ER Positive/HER2 Negative Breast Cancer.

BACKGROUND: The Breast DX Italy prospective study evaluated the impact of the 21-gene recurrence score (RS) result on adjuvant treatment decisions for patients with early breast cancer. MATERIALS AND METHODS: Nine centers (two Hub and seven Spoke centers of the Veneto Oncology Network) participated. Consecutive patients with estrogen receptor positive, human epidermal growth receptor negative, T1-T3, N0-N1 early breast cancer were prospectively registered; only those meeting protocol-defined clinicopathological "intermediate risk" criteria were eligible for the RS test. Pre-RS and post-RS physicians' treatment recommendations and treatment actually received were collected. RESULTS: A total of n = 124 N0 and n = 126 N1 patients underwent the RS assay. The majority had Grade 2 tumors (71%); median age was 55 years, median tumor size was 16 mm, and median Ki67 expression was 20%. Patients enrolled at Hub centers presented higher-risk features. The distribution of RS results was <18 (60.8%), 18-30 (32.4%), and >30 (6.8%). The indication before RS was hormonal therapy (HT) alone in 52% of cases. An indication before RS of chemotherapy (CT)+HT was more frequent for patients with N1 versus N0 tumors (57% vs. 39%, p = .0035) and for patients enrolled at Hub versus Spoke centers (54% vs. 36%, p = .007).The overall rate of change in treatment decision was 16% (n = 40), mostly from CT+HT to HT (n = 30). According to nodal status, rate of change in treatment decision was 12% for the N0 cohort and 20% for the N1 cohort. The proportion of patients recommended to CT+HT was significantly reduced from before to after RS (48% to 40%, p < .0016), especially in the N1 cohort (57% to 45%, p = .0027) and at Hub centers (54% to 44%, p = .001). CONCLUSION: Despite frequent indication of HT before RS, the use of the RS assay further contributed to sparing CT, especially for patients with N1 tumors and at Hub centers. IMPLICATIONS FOR PRACTICE: This study shows that, although a high proportion of patients were recommended to receive endocrine treatment alone before knowing the recurrence score (RS) assay, the RS test further contributed in sparing chemotherapy for some of these patients, especially in case of the N1 stage or for patients enrolled at referral centers. These data highlight the need for further work in collaboration with health authorities and companies in order to define strategies for the implementation of the use of RS testing in clinical practice in the Italian setting.

Incident Cerebral Microbleeds in a Cohort of Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: We aimed to identify prognostic and associated factors of incident cerebral microbleeds (CMBs) in intracerebral hemorrhage (ICH) survivors. METHODS: Observational prospective cohort of 168 ICH survivors who underwent 1.5T magnetic resonance imaging at ICH onset and during follow-up (median scan interval, 3.4; interquartile range, 1.4-4.7) years. We used logistic regression adjusted for age, sex, and scan interval. Analyses were stratified according to the index ICH location (58 lobar ICH, 103 nonlobar ICH, excluding patients with multiple or unclassifiable ICH). RESULTS: Eighty-nine (53%) patients had CMBs at ICH onset, and 80 (48%) exhibited incident CMBs during follow-up. Predictors of incident CMBs at ICH onset were ≥1 CMBs (adjusted odds ratio [aOR], 2.27; 95% confidence interval [CI], 1.18-4.35), old radiological macrohemorrhage (aOR, 6.78; 95% CI, 2.76-16.68), and CMBs in mixed location (aOR, 3.73; 95% CI, 1.67-8.31). When stratifying by ICH location, incident CMBs were associated in nonlobar ICH with incident lacunes (aOR, 2.86; 95% CI, 1.04-7.85) and with the use of antiplatelet agents (aOR, 2.89; 95% CI, 1.14-7.32). In lobar ICH, incident CMBs were associated with incident radiological macrohemorrhage (aOR, 9.76; 95% CI, 1.07-88.77). CONCLUSIONS: Prognostic and associated factors of incident CMBs differed according to the index ICH location. Whereas in lobar ICH, incident CMBs were associated with hemorrhagic biomarkers, in nonlobar ICH, ischemic burden also increased. CMBs may be interesting biomarkers to monitor in randomized trials on restarting antithrombotic drugs after ICH.

Prognostic Factors for Cognitive Decline After Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Stroke and dementia are closely related, but no prospective study ever focused on poststroke cognitive decline in patients with intracerebral hemorrhage (ICH). We aimed to determine prognostic factors for cognitive decline in patients with ICH. METHODS: We prospectively included 167 consecutive ICH survivors without preexisting dementia from the Prognosis of Intra-Cerebral Hemorrhage (PITCH) cohort. Median follow-up was 4 years (interquartile range, 2.3-5.4). We explored factors associated with cognitive decline using linear mixed models. Cognitive decline was determined based on repeated mini-mental state examination. We investigated each prognostic factor separately in univariate models. Next, we constructed clinical and radiological multivariable models. In a sensitivity analysis, we excluded patients with preexisting cognitive impairment. RESULTS: Median age was 64 (interquartile range, 53-75) years, 69 (41%) patients were women, and median mini-mental state examination at 6 months was 27 (interquartile range, 23-29). Overall, 37% of the patients declined during follow-up. Factors associated with cognitive decline in univariate analyses were previous stroke or transient ischemic attack, preexisting cognitive impairment, microbleed presence, severity of white matter hyperintensities, and severity of cortical atrophy. In multivariable analyses, previous stroke or transient ischemic attack (ß [SE], -0.55 [0.23]; P<0.05), preexisting cognitive impairment (ß [SE], -0.56 [0.25]; P<0.01), and severity of cortical atrophy (ß [SE], -0.50 [0.19]; P<0.01) remained independent prognostic factors. In patients without preexisting cognitive impairment (n=139), severity of cortical atrophy (ß [SE], -0.38 [0.17]; P<0.05) was the only prognostic factor for future cognitive decline. CONCLUSIONS: Prognostic factors for cognitive decline after ICH are already present when ICH occurs, suggesting a process of ongoing cognitive impairment instead of new-onset decline induced by the ICH itself.

The CAVE score for predicting late seizures after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Seizures are a common complication of intracerebral hemorrhage (ICH). We developed a novel tool to quantify this risk in individual patients. METHODS: Retrospective analysis of the observational Helsinki ICH Study (n=993; median follow-up, 2.7 years) and the Lille Prognosis of InTra-Cerebral Hemorrhage (n=325; 2.2 years) cohorts of consecutive ICH patients admitted between 2004 and 2010. Helsinki ICH Study patients' province-wide electronic records were evaluated for early seizures occurring within 7 days of ICH and among 7-day survivors (n=764) for late seizures (LSs) occurring >7 days from ICH. A Cox regression model estimating risk of LSs was used to derive a prognostic score, validated in the Prognosis of InTra-Cerebral Hemorrhage cohort. RESULTS: Of the Helsinki ICH Study patients, 109 (11.0%) had early seizures within 7 days of ICH. Among the 7-day survivors, 70 (9.2%) patients developed LSs. The cumulative risk of LSs was 7.1%, 10.0%, 10.2%, 11.0%, and 11.8% at 1 to 5 years after ICH, respectively. We created the CAVE score (0-4 points) to estimate the risk of LSs, with 1 point for each of cortical involvement, age<65 years, volume>10 mL, and early seizures within 7 days of ICH. The risk of LSs was 0.6%, 3.6%, 9.8%, 34.8%, and 46.2% for CAVE scores 0 to 4, respectively. The c-statistic was 0.81 (0.76-0.86) and 0.69 (0.59-0.78) in the validation cohort. CONCLUSIONS: One in 10 patients will develop seizures after ICH. The risk of this adverse outcome can be estimated by a simple score based on baseline variables.

Petal-shaped corneal pattern in a patient with posterior amorphous corneal dystrophy.

Purpose: To describe the petal-shaped corneal pattern in a patient with posterior amorphous corneal dystrophy. Observation: A 19-year-old male affected by Graves' disease presented corneal grey sheet-like opacities and high hyperopia. Corneal topography showed reduced k-values compatible with cornea plana and reduced corneal pachymetry. The anterior segment optical coherence tomography showed a hyperreflective band at the posterior stroma-Descemet-Endothelium layers in both eyes. Slit lamp examination with cobalt blue filter showed a corneal pattern resembling a petal in right eye; the pattern was similar but incomplete in left eye. Conclusion & importance: After an exhaustive literature review conducted from October 1st to 30th, 2023, utilizing online databases like PubMed and Google Scholar, and employing keywords such as "Corneal Dystrophy," "Slit Lamp," "Cornea," and "Posterior Amorphous Corneal Dystrophy," we found no previous reports detailing the whole corneal pattern using a blue cobalt filter on the slit lamp in cases of posterior amorphous corneal dystrophy. Cobalt blue filter was an effective method for capturing the full photographic corneal pattern of the patient posterior amorphous corneal dystrophy.

Noninvasive Ocular Surface Workup in Patients with Meibomian Gland Dysfunction Using Microwave-Heated Eye Bag.

Purpose: To report the outcomes of a novel microwave heating device (Blepha EyeBag®) used serially for the treatment of meibomian gland dysfunction (MGD). Patients and Methods: This prospective single center study was conducted at University Magna Graecia of Catanzaro. Patients were instructed to apply the compress twice daily for 15 days and once per day every two days, as reported in the package insert. Outcome measures were i) ocular surface disease index (OSDI) score, ii) tear meniscus height (TMH), iii) non-invasive keratograph break-up time (NIKBUT) (first and average), iv) meiboscore, v) bulbar redness. Evaluations were performed at baseline (T0) after 15 days (T1) and after 45 days of therapy (T2). Results: Overall, 19 patients with MGD (8 males, 11 females; mean age 64.58 ± 9.72 years) were included. The mean value of OSDI score showed a significant decrease from 28.16 ± 17.46 at T0 to 13.69 ± 7.62 at T2 (p=0.008). The mean value of NIKBUT first significantly increased from 6.67 ± 3.51 seconds (s) at T0 to 10.46 ± 4.64 at T2 (p=0.0121); in parallel, the mean value of NIKBUT average increased significantly from 11.09 ± 4.15 s at T0 to 14.95 ± 4.85 at T2 (p=0.0049). No significant differences were detected at each time point for bulbar redness, meiboscore and TMH. Throughout the entire study, no adverse events were recorded. Conclusion: The microwave-heated eye bag treatment is both safe and effective for treatment of MGD, being able to significantly ameliorate both patient-reported symptoms and tear film stability.

A Novel Noninvasive Screening Tool for Dry Eye Disease.

PURPOSE: To assess the feasibility and the diagnostic accuracy of the new tool, DEvice© (AI, Rome, Italy), for screening patients with dry eye disease (DED). METHODS: This study was performed at the University Magna Græcia of Catanzaro. Enrolled patients were classified as affected by DED (group 1) or not (group 2) using an already validated tool (Keratograph 5M, Oculus, Germany), evaluating the noninvasive keratograph breakup time (NIKBUT), tear meniscus height (TMH), meibomian gland loss (MGL), and bulbar redness. All the patients were then examined by means of DEvice©, which allowed the measurement of the relative humidity (RH) and temperature of the ocular surface. Symptoms were scored using the Ocular Surface Disease Index (OSDI) questionnaire. RESULTS: Overall, 40 patients (17 males and 23 females, mean age 38.0 ± 17.1 years) were included: of these, 20 belonged to group 1 and the remaining 20 to group 2. Using Keratograph 5M, significant differences between groups 1 and 2 were detected for NIKBUT-first (respectively, 4.97 ± 1.85 vs. 13.95 ± 4.8 s; p < 0.0001) and for NIKBUT-average (10.55 ± 4.39 vs. 15.96 ± 4.08 s; p = 0.0003). No statistically significant changes were detected for TMH (p = 0.565), MGL (p = 0.051), and bulbar redness (p = 0.687). Using Device©, a statistically significant higher value of RH was found in group 1 compared to group 2 (respectively, 85.93 ± 10.63 vs. 73.05 ± 12.84%; p = 0.0049). A statistically significant correlation was found between RH and OSDI (r = 0.406; p = 0.009). The value RH showed a discriminating power to detect DED with an AUC = 0.782 (standard error 0.07264; 95% CI 0.6401-0.9249; p = 0.0022). CONCLUSIONS: The DEvice© can effectively discriminate DED patients from healthy subjects. The parameter RH showed good sensitivity, making this tool ideal for a fast and noninvasive DED screening.

Feasibility of Tear Meniscus Height Measurements Obtained with a Smartphone-Attachable Portable Device and Agreement of the Results with Standard Slit Lamp Examination.

PURPOSE: We aimed to evaluate the feasibility of using a novel device, the Smart Eye Camera (SEC), for assessing tear meniscus height (TMH) after fluorescein staining and the agreement of the results with measurements obtained using standard slit lamp examination. METHODS: TMH was assessed using both SEC and conventional slit lamp examination. The images were analyzed using the software ImageJ 1.53t (National Institutes of Health, Bethesda, MD, USA). A common measurement unit scale was established based on a paper strip, which was used as a calibration marker to convert pixels into metric scale. A color threshold was applied using uniform parameters for brightness, saturation, and hue. The images were then binarized to black and white to enhance the representation of the tear menisci. A 2 mm area around the upper and lower meniscus in the central eye lid zone was selected and magnified 3200 times to facilitate manual measurement. The values obtained using SEC were compared with those obtained with a slit lamp. RESULTS: The upper and lower TMH values measured using the SEC were not statistically different from those obtained with a slit lamp (0.209 ± 0.073 mm vs. 0.235 ± 0.085, p = 0.073, and 0.297 ± 0.168 vs. 0.260 ± 0.173, p = 0.275, respectively). The results of Bland-Altman analysis demonstrated strong agreement between the two instruments, with a mean bias of -0.016 mm (agreement limits: -0.117 to 0.145 mm) for upper TMH and 0.031 mm (agreement limits: -0.306 to 0.368 mm) for lower TMH. CONCLUSIONS: The SEC demonstrated sufficient validity and reliability for assessing TMH in healthy eyes in a clinical setting, demonstrating concordance with the conventional slit lamp examination.

Noninvasive screening of ocular surface disease in otherwise healthy patients scheduled for cataract surgery.

PURPOSE: To evaluate prevalence and characteristics of pathological ocular surface findings in healthy patients undergoing cataract surgery using a noninvasive ocular surface workup and a validated questionnaire. DESIGN: Prospective single-centre study (sub-analysis clinical trial no. NCT05754437). METHODS: Healthy patients undergoing senile cataract surgery were screened preoperatively by Oculus Keratograph (K5 M; Oculus GmbH, Wetzlar, Germany) for the evaluation of tear meniscus height (TMH), non-invasive keratograph break-up time (NIKBUT), and meibomian gland dropout. Ocular discomfort symptoms were scored by ocular surface disease index (OSDI) questionnaire. RESULTS: 120 eyes of 120 patients (62 females, 58 males; mean age 73.85 years, range 47-91 years) were included. All patients had at least 1 abnormal finding, while 19 (15.8%; 95% CI [0.09-0.22]) had alterations of all parameters. In detail, 39 patients (32.5%; 95% CI [0.24-0.41]) had pathological TMH (mean 0,15 mm [0.03 SD]), 102 (85%; 95% CI [0.79-0.91]) had pathological NIKBUT (mean 3.64 s [2.63 SD]), 117 (97.5%; 95% CI [0.95-1]) had some degree of gland dropout (mean 1.62 [0.70 SD]), 78 patients (65%; 95% CI [0.56-0.74]) had pathological OSDI scores (mean 28.63 [15.08 SD]). Using TFOS DEWS II criteria, 66 patients (55%; 95% CI [0.42-0.60]) resulted affected by dry eye. CONCLUSIONS: This quick noninvasive screening documented the high prevalence of pathological ocular surface parameters in patients without risk factors or previous diagnosis of dry eye who are scheduled for cataract surgery.

Ophthalmic Manifestations in Patients with Blood Malignancies.

Ocular complications can occur in up to 90% of patients with blood malignancies. Such complications range from direct infiltration to local hemostatic imbalance and treatment-related toxicity. This narrative review is based on a systematic computerized search of the literature conducted until January 2024 and examines the common ocular complications associated with blood cancers. Ocular complications from primary disease include mass effects from ocular adnexal lymphomas and intraocular lymphomas, with B-cell lymphomas accounting for 95% of primary ocular presentations. Secondary disease involvement from systemic hematological malignancies can lead to a wide range of ocular manifestations, such as leukemic retinopathy. Furthermore, toxicity from antineoplastic therapies and ocular graft versus host disease (oGVHD) after hematopoietic stem cell transplantation present additional risks to ocular health. In conclusion, ocular complications in blood cancer patients are an integral part of patient management, requiring regular ophthalmic evaluations and close collaboration between oncologists and ophthalmologists. Advances in therapy and an increased focus on early symptom recognition are essential for preserving vision and enhancing patient quality of life.

A Novel Ophthalmic Solution Containing Glicopro® Complex for the Treatment of Patients with Dry Eye Disease: Results from a Pilot Study.

(1) Background: Dry eye disease (DED) is a multifactorial ocular surface disease characterized by an imbalance in ocular surface homeostasis, and tear substitutes constitute the first line of treatment. The present study aimed to evaluate the changes in the signs and symptoms of patients with DED treated with a novel tear substitute containing the GlicoPro® complex. (2) Methods: Patients with DED not successfully responding to other tear substitutes were enrolled and treated with a novel ophthalmic solution (two drops four times daily). Patients were examined before starting the study treatment (T0) and after 30 (T1) and 60 (T2) days of treatment by means of Keratograph for the evaluation of the following: (i) tear meniscus height (TMH); (ii) noninvasive Keratograph break-up time (NIKBUT); (iii) bulbar redness; and (iv) infrared meibography. The SANDE questionnaire was administered to assess ocular discomfort symptoms. Analysis of the tear content of proenkephalin and Met/Leu-enkephalin was also performed. (3) Results: At T2, a significant improvement in NIKBUT first, average, and class, TMH, and SANDE score was found. The tear content of proenkephalins was significantly higher at T1, whereas processed active Met/Leu-enkephalins increased at both T1 and T2. (4) Conclusions: Our novel tear substitute based on GlicoPro® resulted in a significant improvement in ocular discomfort symptoms, tear volume, and stability in the patients treated. The increase in active peptides processed in tears may represent the pathophysiological substrate underlying this finding.

Incidence and predictors of late seizures in intracerebral hemorrhages.

BACKGROUND AND PURPOSE: To identify incidence and predictors of late seizures (LS, occurring >1 week of stroke) in a cohort of patients with intracerebral hemorrhage (ICH). METHODS: Prospective cohort of consecutive adults with spontaneous ICH. Incidence and predictors were identified with Cox regression. We included multivariate analyses on MRI biomarkers (global cortical atrophy, leukoaraiosis, brain microbleeds). RESULTS: Our study population consisted of 325 patients: 54% men, median age 70 years (interquartile range, 58-79). During 778 person-years of follow-up, the incidence rate was 4 new cases/100 person-years (95% confidence interval, 3-6). The median delay between ICH and LS was 9 months (interquartile range, 3-23). The only factor independently associated with the occurrence of LS was a cortical involvement of the ICH (hazard ratio, 2.8; 95% confidence interval, 1.3-6.1). Concerning MRI biomarkers, multivariate analyses found lobar brain microbleeds to be associated with LS (hazard ratio, 2.4; 95% confidence interval, 1.1-5.4), especially if ≥ 3 (hazard ratio, 2.7; 95% confidence interval, 1.1-6.8). LS were associated with a worse functional outcome after 3 years of follow-up (P=0.009). CONCLUSIONS: LS frequently occur >9 months after ICH onset, imposing a long-term follow-up. The association of lobar brain microbleeds with the risk of LS might suggest a link with the underlying vasculopathy (cerebral amyloid angiopathy).

Intra-arterial thrombectomy versus standard intravenous thrombolysis in patients with anterior circulation stroke caused by intracranial arterial occlusions: a single-center experience.

BACKGROUND: Severely impaired patients with persisting intracranial occlusion despite standard treatment with intravenous (IV) administration of recombinant tissue plasminogen activator (rtPA) or presenting beyond the therapeutic window for IV rtPA may be candidates for interventional neurothrombectomy (NT). The safety and efficacy of NT by the Penumbra System (PS) were compared with standard IV rtPA treatment in patients with severe acute ischemic stroke (AIS) caused by large intracranial vessel occlusion in the anterior circulation. METHODS: Consecutive AIS patients underwent a predefined treatment algorithm based on arrival time, stroke severity as measured by the National Institutes of Health Stroke Scale (NIHSS) score, and site of arterial occlusion on computed tomographic angiography (CTA). NT was performed either after a standard dose of IV rtPA (bridging therapy [BT]) or as single treatment (stand-alone NT [SAT]). Rates of recanalization, symptomatic intracranial bleeding (SIB), mortality, and functional outcome in NT patients were compared with a historical cohort of IV rtPA treated patients (i.e., controls). Three-month favourable outcome was defined as a modified Rankin Scale (mRS) score ≤2. RESULTS: Forty-six AIS patients were treated with NT and 51 with IV rtPA. The 2 groups did not differ with regard to demographics, onset NIHSS score (18.5±4 v 17±5; P=.06), or site of intracranial occlusion. Onset-to-treatment time in the NT and IV rtPA groups was 230 minutes (±78) and 176.5 (±44) minutes, respectively (P=.001). NT patients had significantly higher percentages of major improvement (≥8 points NIHSS score change at 24 hours; 26% v 10%; P=.03) and partial/complete recanalization (93.5% v 45%; P<.0001) compared to controls. Treatment by either SAT or BT similarly improved the chance of early recanalization and early clinical improvement. No significant differences were observed in the rate of SIB (11% v 6%), 3-month mortality (24% v 25%), or favorable outcome (40% v 35%) between NT and IV rtPA patients. CONCLUSIONS: Despite significantly delayed time of intervention, NT patients had higher rates of recanalization and early major improvement, with no differences in symptomatic intracranial hemorrhages. Early NIHSS score improvement did not translate into better 3-month mortality or outcome. NT seems a safe and effective adjuvant treatment strategy for selected patients with severe AIS secondary to large intracranial vessel occlusion in the anterior circulation.

Phacoemulsification Under the Complex Dua Layer-Descemet-Endothelium for Combined Cataract Surgery and Penetrating Keratoplasty After Failed Deep Anterior Lamellar Keratoplasty.

PURPOSE: The aim of this study was to report the surgical management of an eye with a cataract and a failed deep anterior lamellar keratoplasty (DALK) graft. Given the null visualization of the anterior chamber, instead of performing penetrating keratoplasty (PK) combined with open-sky extracapsular extraction, the cleavage plane of the previous DALK was used to expose the transparent complex including Dua layer (DL)-Descemet membrane (DM)-endothelium and to perform phacoemulsification in a closed system; then, PK was completed after the surgical removal of the complex DL-DM-endothelium. METHODS: This study is a case report. RESULTS: A 45-year-old woman with corneal opacity due to Acanthamoeba keratitis underwent multiple (n = 2) DALK surgeries. The second DALK graft underwent failure, with the development of severe corneal edema; a dense opacity of the lens was also present. The patient was scheduled for combined PK and cataract surgery. Because the cornea was too opaque to allow closed-system cataract surgery, a partial trephination was performed with the purpose of reopening the old donor-host junction and finding the deep cleavage plane. This maneuver permitted the exposition of the complex DL-DM-endothelium that was completely transparent, thus allowing standard phacoemulsification using the phaco-chop technique. A full-thickness corneal graft was then positioned and sutured. CONCLUSIONS: This case confirms the toughness of the complex DL-DM-endothelium and reveals the transparency of this complex even in the presence of a failed endothelium, thus highlighting distinct advantages of our surgical approach over the conventional one involving PK combined with open-sky extracapsular extraction.

Impact of topographic localization of corneal ectasia on the outcomes of deep anterior lamellar keratoplasty employing large (9 mm) versus conventional diameter (8 mm) grafts.

OBJECTIVES: Visual and topographic outcomes of large (9.0 mm) versus conventional (8.0 mm) deep anterior lamellar keratoplasty (DALK) for the treatment of keratoconus (KC) were compared in relation to the different localization of the corneal ectasia (within or beyond the central 8.0 mm). METHODS: This is a retrospective, comparative case series. Preoperatively, the topographic extension of the conus was calculated by measuring the distance from the geometric center of the cornea and the outermost point of the corneal ectasia (ectasia <8.0 mm, group A; ectasia ≥8.0 mm, group B). DALK was performed using both small grafts (8.0 mm, group 1) and large grafts (9.0 mm, group 2). Best-corrected visual acuity and topographic astigmatism were evaluated preoperatively (T0) and postoperatively after complete suture removal (1 year, T1). RESULTS: Data from 224 eyes of 196 patients (mean age 37.6 ± 15.1 years) were evaluated. Topographic astigmatism improved from T0 to T1 (4.94 ± 2.92 diopters (D) [95% CI, 4.56-5.33] vs 4.19 ± 2.45 D [95% CI, 3.87-4.51], p = 0.001). There was no significant difference in postoperative topographic cylinder between group 1 and group 2 when considering eyes with corneal ectasia <8.0 mm (group 1 A, 4.15 ± 2.19 D [95% CI, 3.64-4.66] vs group 2 A, 3.65 ± 2.13 D [95% CI, 2.92-4.38], p = 0.14); conversely, the difference was significant considering eyes with corneal ectasia ≥8.0 mm (group 1B, 4.74 ± 2.90 D [95% CI, 4.09-5.38] vs group 2B, 3.68 ± 1.94 D [95% CI, 3.10-4.26], p = 0.02). CONCLUSIONS: Large 9.0-mm DALK provided better anatomical outcomes compared to conventional 8.0-mm DALK, particularly in eyes with corneal ectasia extending beyond the central 8.0 mm.

Comparative performance of humans versus GPT-4.0 and GPT-3.5 in the self-assessment program of American Academy of Ophthalmology.

To compare the performance of humans, GPT-4.0 and GPT-3.5 in answering multiple-choice questions from the American Academy of Ophthalmology (AAO) Basic and Clinical Science Course (BCSC) self-assessment program, available at https://www.aao.org/education/self-assessments . In June 2023, text-based multiple-choice questions were submitted to GPT-4.0 and GPT-3.5. The AAO provides the percentage of humans who selected the correct answer, which was analyzed for comparison. All questions were classified by 10 subspecialties and 3 practice areas (diagnostics/clinics, medical treatment, surgery). Out of 1023 questions, GPT-4.0 achieved the best score (82.4%), followed by humans (75.7%) and GPT-3.5 (65.9%), with significant difference in accuracy rates (always P < 0.0001). Both GPT-4.0 and GPT-3.5 showed the worst results in surgery-related questions (74.6% and 57.0% respectively). For difficult questions (answered incorrectly by > 50% of humans), both GPT models favorably compared to humans, without reaching significancy. The word count for answers provided by GPT-4.0 was significantly lower than those produced by GPT-3.5 (160 ± 56 and 206 ± 77 respectively, P < 0.0001); however, incorrect responses were longer (P < 0.02). GPT-4.0 represented a substantial improvement over GPT-3.5, achieving better performance than humans in an AAO BCSC self-assessment test. However, ChatGPT is still limited by inconsistency across different practice areas, especially when it comes to surgery.

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.

Outcomes of low-level light therapy before and after cataract surgery for the prophylaxis of postoperative dry eye: a prospective randomised double-masked controlled clinical trial.

BACKGROUND: Despite increasing evidence shows that optimising ocular surface before cataract surgery is fundamental in patients with pre-existing dry eye disease (DED) to achieve the desired postoperative outcomes, the prophylactic treatment of healthy patients undergoing surgery aiming at preventing iatrogenic DED is worth investigating. METHODS: This was a prospective, interventional, randomised, controlled, double-masked clinical trial. Patients were randomly assigned 1:1 to receive either low-level light therapy (LLLT) or sham treatment (LLLT with a power output <30%). Patients underwent two treatment sessions: 7±2 days before cataract surgery (T0) and 7±2 days after (T1). Outcome measures evaluated 30±4 days after surgery (T2) included Ocular Surface Disease Index (OSDI) questionnaire, non-invasive break-up time (NIBUT), tear meniscus height, meibomian gland loss (MGL) and redness score. RESULTS: Out of 153 patients randomised to receive LLLT (n=73) or sham treatment (n=80), 131 (70 men, 61 women, mean age 73.53±7.29 years) completed regularly the study. Patients treated with LLLT had significantly lower OSDI scores compared with controls at T1 and T2 (respectively, 7.2±8.8 vs 14.8±13.0 and 9.0±9.0 vs 18.2±17.9; both p<0.001), higher NIBUT values at T2 (12.5±6.6 vs 9.0±7.8; p=0.007) and lower MGL Meiboscore values at T1 (1.59±0.70 vs 1.26±0.69; p=0.008). Unlike controls, patients treated with LLLT had significantly lower OSDI scores and higher NIBUT values at T2 compared with T0 (respectively, 9.0±9.0 vs 21.2±16.1; p<0.001 and 12.5±6.6 vs 9.7±7.2; p=0.007). CONCLUSION: Two sessions of LLLT performed before and after cataract surgery were effective in ameliorating tear film stability and ocular discomfort symptoms. TRIAL REGISTRATION NUMBER: NCT05754437.