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.

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.

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.

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.

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.

Association of tumor-infiltrating lymphocytes with recurrence score in hormone receptor-positive/HER2-negative breast cancer: Analysis of four prospective studies.

BACKGROUND: The clinical value of tumor infiltrating lymphocytes (TILs) in hormone receptor-positive (HR+)/HER2- breast cancer (BC) may be unearthed by focusing on more biologically aggressive tumors. Here we deepen and describe the correlation between RS and TILs, proposing an immuno-genomic model for HR+ /HER2- BC. METHODS: We enrolled T1-T3, N0-N1 BC patients with available RS® and TILs in the context of four multicenter, prospective studies. RS® and TILs were considered as continuous and categorical variables. RS® was categorized into: 0-10 (low risk), 11-25 (intermediate risk) and 26-100 (high risk); TILs were categorized into: low TILs (0-10%), intermediate TILs (11-59%) and high TILs (60-100%). RESULTS: 811 patients were included. RS distribution was (n = 810): low risk 22.0%, intermediate risk 61.2%, high risk 16.8%. TIL distribution was (n = 455): low TILs 84.6%, intermediate TILs 13.6% and high TILs 1.8%. A significant, weak positive, linear correlation was found between continuous TILs and RS (Pearson coefficient=0.223, p < 0.001). When considering RS and TILs categories, tumors with intermediate/high TIL levels significantly enriched the high RS subgroup (p = 0.006). This was confirmed both within Luminal A and Luminal B cohorts. Among high-RS patients, 16.7% of Luminal A and 26.7% of Luminal B tumors had intermediate/high TILs. CONCLUSIONS: We observed that RS® and TILs capture only slightly overlapping information on the biology of HR+ /HER2- tumor microenvironment. We demonstrated the feasibility of combining RS and TILs into a composite immuno-genomic model, which may serve the purpose of guiding and focalizing patient selection in the further development of immunotherapy strategies for Luminal-like disease.

Neoadjuvant Systemic Therapy in Early Breast Cancer: Results of a Prospective Observational Multicenter BRIDE Study.

To evaluate the rate of early breast cancer (EBC) patients treated with neoadjuvant systemic therapy (NAT) in Italy, criteria of patient selection and types of therapies delivered, an analysis of 1276 patients with stage I-II-III was conducted out of 1633 patients enrolled in the multicenter prospective observational BRIDE study. A total of 177 patients (13.9%) were treated with NAT and 1099 (85.9%) with surgery; in multivariate analysis, menopausal status, cT, cN, grade, HER2-positive and Triple negative (TN) subgroups were significantly associated with the decision to administer NAT. The type of NAT delivered was influenced by EBC subtype. NAT was administered to 53.2% of HER2+/HR-negative, 27.9% of HER2+/HR+, 7.1% of HER2-negative/HR+ and 30.3% of TN EBC patients. The pCR rates were similar to the ones reported in the literature: 74.2% in HER2+/HR-negative, 52.3% in HER2+/HR+, 17.2% in HER2-negative/HR+ and 37.9% in TN. In clinical practice, patient and tumor characteristics influenced oncologists in the decision to administer NAT in EBC and in the choice of the type of systemic therapy, according to ESMO and AIOM Guidelines. Currently, it is recommended always to evaluate the use of NAT in EBC, mainly in HER2+ and TN patients, considering that pCR is associated with significantly better survival of the patient and that effective therapies are now available for residual disease.

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.

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.

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.

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.

Optimizing CDK4/6 inhibitors in advanced HR+/HER2- breast cancer: A personalized approach.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are now a backbone of treatment for hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. CDK4/6i plus ET is more effective than ET alone in this setting; however, the risk of grade 3-4 adverse events also increases. Approved agents in this class have similar efficacies, but important differences due to their structural and pharmacological properties. We review biomarkers and discuss determinants to inform a rational approach to therapy choice when selecting the most appropriate ET and CDK4/6i partners. We also identify subgroups that may benefit from specific ET-CDK4/6i combinations and discuss strategies to overcome resistance. This personalized approach aims to minimize treatment-related toxicities that may affect patient QoL and compliance, and ultimately therapy efficacy.

Outcomes of Abrupt Switch to Bevacizumab of Patients Undergoing Aflibercept Intravitreal Injections for Neovascular Age-Related Macular Degeneration in a Tertiary Center in Lombardy, Italy: A Real-Life Retrospective Analysis.

PURPOSE: To assess real-life anatomical and functional outcomes of switch to bevacizumab in patients undergoing aflibercept intravitreal injections for nAMD. METHODS: Retrospective chart review of all patients diagnosed with nAMD and undergoing intravitreal injections of aflibercept who switched to bevacizumab after the resolution XI/1986 of Lombardy Region. RESULTS: Among 128 patients undergoing intravitreal injections, a total of 29 eyes of 29 patients met all inclusion criteria and were included in the statistical analysis. Best corrected visual acuity and central macular thickness did not change significantly (p > 0.05) between baseline, after the loading phase, and at the last follow-up. CONCLUSION: Switching to bevacizumab has been safe and efficacious in patients responding to the loading phase. According to our results, the restrictions imposed by Lombardy Region did not cause any harm to patients undergoing intravitreal anti-VEGF injections.

Trigeminal Metastasis of Malignant Melanoma: Clinical, Neuroradiological, and Pathological Features. A Case Report.

INTRODUCTION: Perineural spread of malignant melanoma (MM) along cranial nerves is a rare complication of MM of the head and neck. CASE REPORT: A 78-year-old man presented with untreatable facial pain and cutaneous hypoesthesia in V2/V3 branches of right trigeminal nerve. Six months earlier patient removed a lentigo maligna melanoma in his right upper lip and a MM in his right gingiva. Brain magnetic resonance imaging showed pathologic thickening of the right maxillary and mandibular nerves and of the intracranial trigeminal nerve. Infraorbital nerve biopsy confirms MM neural metastasis. BRAFV600E mutation was identified only in the lentigo maligna melanoma. Patient was treated with brain proton therapy but 5 months later developed sensorimotor deficit of his right arm because of a cervical metastasis. CONCLUSIONS: In patients presenting with atypical facial pain and history of head and neck melanoma a trigeminal spreading should be considered. Magnetic resonance imaging can detect early perineural spread and target biopsy.

Everolimus plus aromatase inhibitors as maintenance therapy after first-line chemotherapy: Final results of the phase III randomised MAIN-A (MAINtenance Afinitor) trial.

BACKGROUND: Despite endocrine therapy being the mainstay of treatment for hormone receptor positive (HR+)/HER2- metastatic breast cancer, patients at risk of visceral crisis or doubt for endocrine sensitivity are still offered first-line chemotherapy. Maintenance hormonal therapy is generally offered at the discontinuation of chemotherapy. The MAINtenance Afinitor study is a randomised, phase III trial comparing maintenance everolimus combined with aromatase inhibitors (AIs) versus AI monotherapy in patients with disease control after first-line chemotherapy. METHODS: Patients with stable disease, partial response or complete response after first-line chemotherapy were randomised to everolimus plus AIs (exemestane or letrozole or anastrozole) or to AIs alone. Primary aim was progression-free survival (PFS). Secondary aims included response rate, safety and overall survival (OS). RESULTS: In total, 110 patients were randomised to everolimus + AIs (n = 52) or to AIs (n = 58). Median PFS was 11.0 months (95% confidence interval [CI] 8.1-13.8) in the everolimus + AI arm and 7.2 months (95% CI 4.7-10.9) in the AI monotherapy arm (hazard ratio [HR] 0.71, 95% CI 0.47-1.06). Objective response rate was 22.4% in everolimus + AI arm and 19.2% in AI monotherapy arm. A higher proportion of disease progression as best response was reported in the AI monotherapy arm (28.8% versus 14.3%). Median OS was 35.7 months (95% CI 26.0-47.8) in the combination arm versus 33.5 (95% CI 26.4-42.7) in the AI alone arm (HR 1.0, 95% CI 0.61-1.62). CONCLUSIONS: EVE + AIs did not significantly impact on the outcome of metastatic breast cancer patients deemed suitable for first-line chemotherapy. Also taking into account treatment tolerability, maintenance endocrine therapy remains the standard. TRIAL REGISTRATION: EudraCT: 2013-004153-24.

Cortical superficial siderosis: A prospective observational cohort study.

OBJECTIVE: To determine the prevalence of cortical superficial siderosis (cSS), its clinical and neuroimaging associated markers, and its influence on the risk of recurrent intracerebral hemorrhage (ICH) in a prospective observational ICH cohort. METHODS: We investigated clinical and radiologic markers associated with cSS using multivariable analysis. In survival analyses, we used Cox models to identify predictors of recurrent ICH after adjusting for potential confounders. RESULTS: Of the 258 patients included in the study, 49 (19%; 95% confidence interval [CI] 14%-24%) had cSS at baseline. Clinical factors independently associated with the presence of cSS were increasing age (odds ratio [OR] 1.03 per 1-year increase, 95% CI 1.001-1.06, p = 0.044), preexisting dementia (OR 2.62, 95% CI 1.05-6.51, p = 0.039), and history of ICH (OR 4.02, 95% CI 1.24-12.95, p = 0.02). Among radiologic biomarkers, factors independently associated with the presence of cSS were ICH lobar location (OR 24.841, 95% CI 3.2-14.47, p < 0.001), severe white matter hyperintensities score (OR 5.51, 95% CI 1.17-5.78, p = 0.019), and absence of lacune (OR 4.46, 95% CI 1.06-5.22, p = 0.035). During a median follow-up of 6.4 (interquartile range 2.9-8.4) years, recurrent ICH occurred in 19 patients. Only disseminated cSS (hazard ratio 4.69, 95% CI 1.49-14.71, p = 0.008), not the presence or absence of cSS or focal cSS on baseline MRI, was associated with recurrent symptomatic ICH. CONCLUSION: In a prospective observational cohort of spontaneous ICH, clinical and radiologic markers associated with cSS suggest the implication of underlying cerebral amyloid angiopathy. Disseminated cSS may become a key prognostic neuroimaging marker of recurrent ICH that could be monitored in future clinical trials dedicated to patients with ICH.

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.