Long-term clinical outcome and satisfaction survey in patients with neurotrophic keratopathy after treatment with cenegermin eye drops or amniotic membrane transplantation.

PURPOSE: Neurotrophic keratopathy (NK) is a degenerative corneal disease caused by damage of trigeminal innervation. The purpose of this study is to evaluate the clinical outcomes and patient-reported satisfaction of treatment with amniotic membrane transplantation (AMT) or cenegermin eye drops in patients with NK. METHODS: Clinical charts of patients with NK treated with AMT (group A) or cenegermin eye drops (group B), with at least 12 months of follow-up, were reviewed for demographics, medical history, corneal healing, and disease recurrence. Patient satisfaction was evaluated by a newly developed questionnaire investigating patient's appreciation of treatment of NK (2 items) and satisfaction with NK treatment outcomes (5 items). RESULTS: At the end of treatment, complete corneal healing was observed in 13/15 (86%) patients in group A and in 23/24 (96%) in group B. At 12 months follow-up, 6/13 patients (46%) in group A and 3/23 patients (13%) in group B showed recurrence of NK (p = 0.037). Survival analysis showed that group B remained recurrence free for a significantly longer period of time than the group A (p = 0.028). Patients in group B showed a significantly higher satisfaction when compared with patients in group A (total score: 65.7 ± 15.7 vs 47.4 ± 12.8, p = 0.003), both in terms of patients' appreciation of treatment (78.3 ± 15.9 vs 52.2 ± 30, p = 0.020) and satisfaction with treatment outcomes (60.7 ± 21 vs 45.4 ± 13.3, p = 0.037). CONCLUSIONS: Treatment of NK with cenegermin was associated with long-term maintenance of corneal integrity and a higher degree of patient satisfaction.

COMPARISON BETWEEN SCLERAL BUCKLING AND VITRECTOMY IN THE ONSET OF CYSTOID MACULAR EDEMA AND EPIRETINAL MEMBRANE AFTER RHEGMATOGENOUS RETINAL DETACHMENT REPAIR.

PURPOSE: To investigate the incidence and risk factors for the main complications in patients with rhegmatogenous retinal detachment treated with scleral buckling (SB) or pars plana vitrectomy (PPV). METHODS: A retrospective, comparative, observational study was conducted. The medical records of 107 patients with primary rhegmatogenous retinal detachment who were managed with SB (n = 57) or PPV (n = 50) were reviewed. Scleral buckling was performed using scleral encircling solid silicone band and circumferential solid silicone exoplant to support the break. Pars plana vitrectomy was combined with phacoemulsification in phakic eyes and with scleral encircling in inferior detachments. Follow-ups, including spectral-domain optical coherence tomography examination, were scheduled at 1, 3, and 12 months after surgery. Propensity score matching was used to adjust for potential preoperative selection bias. RESULTS: The overall incidence of postoperative cystoid macular edema (CME) and epiretinal membrane was 14.95% and 30.84%, respectively. Compared with SB, CME was more frequent in the PPV (P = 0.021) and in the PPV pseudophakic eyes (P = 0.027). Postoperative CME was an early, predominantly transient complication and regressed in 67% of SB and in 77% of PPV eyes within 12 months after surgery. No differences were observed regarding epiretinal membrane development. Except for the surgical technique, no preoperative factors associated with CME were identified. A correlation between epiretinal membrane and patients' age was found (P = 0.028). CONCLUSION: The incidence of CME after rhegmatogenous retinal detachment repair was higher in patients who underwent PPV, either alone or combined with phacoemulsification, than in those treated with SB. Epiretinal membrane development was correlated to older age, regardless of the surgical procedure.

Long-term ocular biometric variations after scleral buckling surgery in macula-on rhegmatogenous retinal detachment.

BACKGROUND: Myopic shift and biometric ocular changes have been previously observed after scleral buckling (SB) surgery in rhegmatogenous retinal detachment (RRD), but long term-term outcomes had not yet been explored. The purpose of present study is to evaluate long term ocular biometric changes in patients with primary macula-on RRD treated with SB. METHODS: In this retrospective, observational study, we reviewed the medical records of patients undergoing SB surgery for macula-on RRD. Ocular biometry was performed before and at the most recent visit after surgery. Axial length (AXL), anterior chamber depth (ACD), anterior corneal astigmatism and spherical equivalent in treated eyes were compared before and after surgery as well as with those of fellow eyes. RESULTS: Thirty-four eyes of 17 patients with a mean age of 57.0 ± 8.9 years were included. The mean follow-up duration was 50.9 ± 21.9 months (median 53.0; range 12 to 82 months). A significant postoperative AXL increase of 0.83 mm and a concomitant myopic shift of 1.35 diopters was observed in the operated eyes (p <  0.0001). The preoperative AXL was the only predictive factor of AXL change after surgery (B = 0.152, 95% CI 0.059 to 0.245, ß = 0.668, P = 0.003). Compared to fellow eyes, a postoperative ACD shallowing of 0.1 mm was found in operated eyes (p <  0.05), while there were no long-term changes of anterior corneal astigmatism. CONCLUSIONS: We show that the preoperative AXL is the only predictive factor of AXL increase after SB surgery. Scleral encircling induces a concomitant long-term shallowing of the AC, therefore fourth generation intraocular lens (IOL) power calculation formulae should be used for patients requiring cataract surgery after SB.

Understanding Drivers of Ocular Fibrosis: Current and Future Therapeutic Perspectives.

Ocular fibrosis leads to severe visual impairment and blindness worldwide, being a major area of unmet need in ophthalmology and medicine. To date, the only available treatments are antimetabolite drugs that have significant potentially blinding side effects, such as tissue damage and infection. There is thus an urgent need to identify novel targets to prevent/treat scarring and postsurgical fibrosis in the eye. In this review, the latest progress in biological mechanisms underlying ocular fibrosis are discussed. We also summarize the current knowledge on preclinical studies based on viral and non-viral gene therapy, as well as chemical inhibitors, for targeting TGFß or downstream effectors in fibrotic disorders of the eye. Moreover, the role of angiogenetic and biomechanical factors in ocular fibrosis is discussed, focusing on related preclinical treatment approaches. Moreover, we describe available evidence on clinical studies investigating the use of therapies targeting TGFß-dependent pathways, angiogenetic factors, and biomechanical factors, alone or in combination with other strategies, in ocular tissue fibrosis. Finally, the recent progress in cell-based therapies for treating fibrotic eye disorders is discussed. The increasing knowledge of these disorders in the eye and the promising results from testing of novel targeted therapies could offer viable perspectives for translation into clinical use.

Anterior Segment Optical Coherence Tomography for the Tailored Treatment of Mooren's Ulcer: A Case Report.

Background: Mooren's ulcer (MU) is a rare and debilitating form of peripheral ulcerative keratitis (PUK), characterized by a crescent-shaped ulcer with a distinctive overhanging edge at the corneal periphery. If left untreated, MU can lead to severe complications such as corneal perforation and blindness. Despite various treatment approaches, including anti-inflammatory and cytotoxic drugs, as well as surgical interventions, there is no clear evidence of the most effective treatment due to the lack of randomized controlled trials. AS-OCT is a non-invasive imaging technique that provides high-resolution cross-sectional images of the anterior segment, allowing for accurate evaluation of corneal ulcer characteristics, including depth, extent, and disease progression. Methods: We present the case of a 20-year-old male patient with MU managed using a stepladder approach, which included local and systemic corticosteroids, limbal conjunctival resection, and Cyclosporine A 1% eye drops. The patient underwent consecutive AS-OCT examinations and strict follow-up to tailor systemic and topical therapy. Results: Complete healing of the corneal ulcer with resolution of the inflammatory process was achieved. There was no recurrence of the disease at the 7-month follow-up. AS-OCT demonstrated progressive reorganization and thickening of the stromal tissue until the complete recovery of stromal thickness. Conclusions: The AS-OCT imaging modality allowed for the accurate evaluation of corneal ulcer characteristics, facilitating informed decision-making regarding the use of systemic immunosuppression, surgical interventions, and local immunomodulation and providing detailed and precise assessment of disease progression. This approach enabled a tailored and effective treatment strategy for the patient and played a critical role in guiding the therapeutic approach.

New disposable esthesiometer (KeraSenseⓇ) to improve diagnosis and management of neurotrophic keratitis.

PURPOSE: To validate the use, repeatability, and reproducibility of a new, cost-effective, disposable, sterile device (KeraSenseⓇ, Dompè farmaceutici SpA, Milan Italy) compared to Cochet-Bonnet (CB) esthesiometer. Secondly, to identify a simple, safe, rapid, and low-cost test to diagnose neurotrophic keratitis (NK). METHODS: 16 patients with diagnosis of NK stage I, 25 patients with diabetes mellitus (DM), and 26 healthy subjects were included in the study. Corneal sensitivity (CS) was assessed by CB and KeraSenseⓇ. Repeatability, accuracy, and reproducibility of the novel disposable aesthesiometer were assessed. Specificity, sensitivity, and cut-off value for NK diagnosis were calculated by ROC curve analysis. RESULTS: All NK patients showed a CS ≤ 40 mm, while none of the healthy patients showed a CS value < 50 mm. Significant agreement was found between CB measurements and the single use esthesiometer evaluations of CS (p < 0.001). Repeatability evaluations of the single use esthesiometer showed 100% agreement between different measurements (p < 0.001). Reproducibility evaluations showed 99.6% concordance between different operators (p < 0.001). A 55 mm value of the single use esthesiometer was adequate to exclude an NK diagnosis, while all NK patients showed a value ≤ 35 mm. CONCLUSIONS: Corneal hypo/anaesthesia is considered the hallmark of NK. The use of the novel single-use esthesiometer will allow for a diagnostic improvement in NK, sparing time and guaranteeing patients' safety. Diabetic patients despite normal corneal findings may show impairment of CS, suggesting a preclinical stage of NK, requiring a close follow-up.

Perspective role of Substance P in Amyotrophic Lateral Sclerosis: From neuronal vulnerability to neuroprotection.

The neuropeptide Substance P (SP) and its preferred Neurokinin1 Receptor (NK1R) are known to participate in the physiopathology of neurodegenerative diseases and mainly exert a neuroprotective role. In the present work, we have described the involvement of SP and NK1R in Amyotrophic Lateral Sclerosis (ALS). This was demonstrated by the detection of altered levels of SP in the brain, spinal cord and cerebrospinal fluid (CSF) of patients and preclinical models of ALS, and by its ability to inhibit excitotoxicity-induced neurodegeneration in ALS animal models. These data are supported by results indicating an excitatory effect of SP at the motor neuron (MN) level, which promotes locomotor activity. ALS patients are characterized by a differential susceptibility to MNs degeneration, since sphincters and extraocular muscles are classically spared. It is hypothesized that SP may play a role in the maintenance of the ocular system and the innervation of the pelvic floor by contributing directly or indirectly to the selective resistance of this subset of MNs.

Tomographic and topographic predictive factors of big bubble formation during deep anterior lamellar keratoplasty in keratoconus.

PURPOSE: To identify preoperative predictors of big bubble (BB) formation during deep anterior lamellar keratoplasty (DALK) in patients with keratoconus (KC). METHODS: DESIGN: Retrospective cohort study in an Italian tertiary centre. STUDY POPULATION: Consecutive patients with KC undergoing DALK from January 2021 to July 2023. OBSERVATION PROCEDURE: Tomographic and topographic data including K-max, K-mean, keratometric astigmatism, thinnest point, mean peripheral corneal thickness, difference between the mean peripheral corneal thickness and the thinnest point (peripheral-minimal corneal thickness), position (central/paracentral) and cone area (%), Amsler-Krumeich classification and anterior segment optical coherence tomography (AS-OCT) analysis to assess the severity stage. MAIN OUTCOME MEASURES: Rate of BB formation and type; multivariate logistic regression analysis was used to analyse all preoperative parameters in patients with BB formation versus failure. RESULTS: Pneumatic dissection succeeded in 98 of 140 eyes (70.0%), with 94 type 1 bubbles (67.1%) and four type 2 bubbles (2.9%). BB formation succeeded more frequently in patients with lower K-max (p=0.032), lower K-mean (p=0.010), higher thinnest point (p=0.017), lower peripheral-minimal corneal thickness (p=0.009) and lower Amsler-Krumeich stages (p=0.021). According to the AS-OCT analysis, BB formation was more frequent in the lower stages (p<0.001). After the logistic regression (pseudo-R²=0.176, constant=3.21, 95% CI 1.14 to 5.29, p=0.002), AS-OCT classification was found to be the only factor that predicted BB formation (coefficient=-0.81, 95% CI -1.18 to -0.43, p<0.001). CONCLUSIONS: AS-OCT classification is a reliable predictor for BB formation. Tomographic and topographic analyses indicated that a steeper and more ectatic cornea is more prone to BB failure.

Retrolental cohesive ophthalmic viscoelastic injection for severe subluxated cataracts: a prospective study.

BACKGROUND: To assess anatomical and functional outcomes of retrolental cohesive ophthalmic viscoelastic injection ("Viscolift technique") in patients with severely subluxated cataracts. METHODS: In the present prospective study, we included patients older than 18 years with severely subluxated cataracts and phacodonesis. Full medical history was obtained at the baseline ophthalmological assessment. A single 25-gauge valved trocar was inserted 4 mm from the limbus and a 27G angled cannula was introduced through the trocar into the retrolental space, while cohesive viscoelastic was progressively injected, in order to center and elevate the cataract to facilitate capsulorhexis. After complete phacoemulsification, a 3-piece intraocular lens (IOL) with a scleral fixated Cionni ring or FIL-SSF scleral fixated IOL was implanted. Patients follow-up interval was 6 months after surgery. RESULTS: Thirteen eyes of 13 patients were enrolled in the study, mean age was 61.5 ± 9.4 years and 53.8% were females. The "Viscolift technique" resulted in centered and more stable cataracts in all cases (100%). After complete phacoemulsification, 61.5% of patients were implanted with a 3-piece IOL with Cionni ring, and 38.5% with a FIL-SSF scleral fixated IOL after complete 25G vitrectomy. Mean BCVA improved from 0.5 ± 0.1 LogMar (20/63 Snellen) to 0.1 ± 0.1 LogMar (20/25 Snellen) (p < 0.001) at the last follow-up. No major complications were noted. CONCLUSIONS: The "Viscolift technique" proved to be a safe and effective surgical approach for recentering and elevating subluxated cataracts, thus allowing the surgeon to perform an easier and better-centered capsulorhexis.

Influence of Opacity Depth on Big Bubble Formation During Deep Anterior Lamellar Keratoplasty in Corneal Stromal Scars.

PURPOSE: To identify the key preoperative predictors of big bubble (BB) formation during deep anterior lamellar keratoplasty in patients with corneal stromal scars (CSS). METHODS: This retrospective cohort study included consecutive patients with CSS after infective keratitis who underwent BB-deep anterior lamellar keratoplasty between January 2021 and July 2023 at a tertiary referral center. Topographic and tomographic data were collected to compare the rates and types of BB formations. Anterior segment optical coherence tomography (AS-OCT) was employed to assess the maximum depth of opacity by dividing the stroma into 3 zones of equal thickness: anterior (stage A), mid (stage B), and posterior stroma (stage C). Multivariate logistic regression analysis was performed to identify the potential preoperative predictors of bubble formation. RESULTS: Pneumatic dissection was achieved in 13 of 33 eyes (39.4%), with 11 BB type 1 eyes (33.3%) and 2 BB type 2 eyes (6.1%). According to AS-OCT grading, bubble formation was more frequent with CSS involving more superficial stromal layers (P <0.032). In the eyes with stage C, bubble formation failed 12 out of 14 times (85.7%, P <0.026). Spearman correlation showed that bubble formation was inversely associated with the AS-OCT grading (rho = -0.443, P = 0.001). After logistic regression analysis, AS-OCT grading was found to be the sole factor that predicted bubble formation (coeff. -1.58, confidence interval 95% -3.03 to -0.12, P = 0.034). CONCLUSIONS: Depth of opacity in CSS was the key determinant for predicting the success of pneumatic dissection, as advanced AS-OCT stages are strongly associated with BB failure.

Surgical management of enophthalmos in Duane syndrome.

Duane syndrome is a congenital disorder of eye movement characterized by partial or absent development of the sixth cranial nerve nucleus and/or the sixth nerve itself. Patients often undergo procedures, both surgical and nonsurgical, to correct ocular misalignment and improve the resulting visual problems. We present a case report of a 49-year-old woman with left-sided Duane syndrome who underwent aesthetic surgical correction of enophthalmos.

Platelet-Rich Plasma (PRP) to promote corneal healing in firework-related ocular burn and total limbal stem cell deficiency (LSCD).

PURPOSE: To report the case of persistent corneal epithelial defect in total limbal stem cell deficiency (LSCD) after severe firework-related ocular burn treated with autologous Platelet-Rich Plasma (PRP). CASE DESCRIPTION: A young patient, victim of fireworks trauma, presented with a large persistent epithelial defect affecting the central cornea of his left eye and progressing to stromal melting, in the context of grade VI ocular surface burn with 12 h limbal involvement. Impression cytology to the cornea confirmed a complete LSCD. Assessment of corneal sensitivity by Cochet Bonnet esthesiometer revealed complete corneal anesthesia. Based on progressive clinical worsening under conventional therapy, the patient was started on very pure autologous PRP eye drops obtained using the Hy-Tissue PRP® technology. Six times a day eye drops administration for 30 days was scheduled in the affected eye. At the end of treatment, the epithelial defect had disappeared being replaced by advancing conjunctiva. CONCLUSION: Our findings provide information on management of ocular burns from fireworks, a subject of current interest and concern. Autologous PRP eye drops prepared using the Hy-Tissue PRP® system and administered in the presence of total LSCD and complete corneal anesthesia, prevented corneal stromal melting to progress and allowed the ocular surface epithelial coverage to re-establish. This paved the way for later successful restorative and reconstructive intervention. Also, first description of the Hy-tissue PRP procedure for ophthalmological use is reported.

Cenegermin for the treatment of dry eye disease.

Dry eye disease (DED) is the most common ocular surface disorder affecting millions of people worldwide. Due to its chronic nature, the management of DED still represents a challenge in the ophthalmic practice. Nerve growth factor (NGF), which is expressed along with its high-affinity TrkA receptor on the ocular surface complex, has been widely studied for the treatment of neurotrophic keratopathy, and a novel recombinant human NGF (rhNGF) has recently received full market authorization in this setting. Since NGF has shown in both in vitro and in vivo studies to promote corneal healing, to enhance conjunctival epithelium differentiation and mucin secretion, and to stimulate tear film production and functionality, it could provide potential benefits also in patients with DED. A recent phase II clinical trial has assessed the role of rhNGF in DED patients, demonstrating significant improvements of DED signs and symptoms after 4 weeks of treatment. Further clinical evidence will be provided by the 2 ongoing phase III clinical trials. This review aims at comprehensively illustrating the rationale of use along with the efficacy and safety profile of topical NGF in patients with DED.

Does Patisiran Reduce Ocular Transthyretin Synthesis? A Pilot Study of Two Cases.

BACKGROUND: Variant transthyretin-mediated amyloidosis (ATTR-v) is a well-characterized disease affecting the neurologic and cardiovascular systems. Patisiran has been approved for neurologic involvement as it reduces hepatic synthesis of transthyretin (TTR). Eye involvement is a lateonset feature increasing the risk of glaucoma and cataracts in patients. AIMS: The aim of this case series was to assess whether patisiran can effectively reduce TTR synthesis in such a barrier-protected organ as the eye. METHODS: Two patisiran-treated ATTR-v patients underwent serum and aqueous humor sampling to measure TTR levels detected by SDS-PAGE and immunoblotting. Serum samples were compared to healthy control (HC), whereas aqueous humor samples were compared to non-amyloidotic subjects affected by cataracts and glaucoma. RESULTS: Serum TTR levels representative of hepatic synthesis were sharply lower in treated patients if compared to the HC (-87.5% and -93.75%, respectively). Aqueous humor TTR levels showed mild-tono reduction in treated patients compared to non-amyloidotic subjects with cataracts (-34.9% and +8.1%, respectively) and glaucoma (-41.1% and -2.1%). CONCLUSION: Patisiran does not seem to be as effective in inhibiting ocular TTR synthesis as it is in inhibiting hepatic synthesis. Re-engineering the envelope could allow the drug to target RPE cells thus avoiding any ocular involvement.

Long-term clinical efficacy of topical treatment with recombinant human nerve growth factor in neurotrophic keratopathy: a novel cure for a rare degenerative corneal disease?

BACKGROUND: Neurotrophic keratopathy (NK) is a rare, degenerative ocular disease characterized by reduction or loss of corneal sensitivity and development of non-healing corneal epithelial defects and ulcers. Cenegermin, a recombinant human nerve growth factor (rhNGF) eye drop solution, is the first drug approved for the treatment of NK. The aim of our study is to evaluate the long-term efficacy of this innovative topical treatment in patients with NK. METHODS: Retrospective, consecutive, observational case series study from a single-center setting (Department of Sense Organs, University Sapienza of Rome, Rome, Italy). 18 patients with diagnosis of stage 2 or 3 NK, treated with Cenegermin 20 mcg/ml eye drops were followed for up to 48 months. Recurrence of lesion during follow-up was evaluated at 12, 24, 36, and 48 months. In addition, corneal sensitivity, Schirmer tear test, and visual acuity (VA) were recorded at baseline, end of treatment, and at 12, 24, 36, and 48 months. RESULTS: Three patients experienced recurrence of persistent epithelial defects (PEDs) within 12 months and one patient experienced recurrence of a corneal ulcer within 36 months. Corneal sensitivity was significantly improved at all timepoints (P < 0.05). Significant improvements in visual acuity and tear production were seen at the completion of treatment as well as at 12, 24, and 36 months (P < 0.05) when compared to baseline. CONCLUSIONS: A single 8-week treatment regimen of Cenegermin eye drops has clinical efficacy that can persist for up to 48 months. The long-term clinical utility of treatment with Cenegermin for NK was demonstrated through the low rate of lesion recurrence along with improvements in corneal sensitivity and tear production.

Autophagy-lysosome pathway alteration in ocular surface manifestations in Fabry disease patients.

BACKGROUND: Fabry disease (FD) is a rare X-linked, lysosomal storage disorder caused by mutations in the alpha-galactosidase gene and characterized by neurological, cutaneous, renal, cardiovascular, cochleo-vestibular and ocular manifestations. The aim of this study is to characterize morphological, functional and autophagy-lysosome pathway alterations of the ocular surface in FD patients. METHODS: Eleven subjects with a diagnosis of FD and fifteen healthy control subjects were examined. All patients underwent ocular surface slit lamp examination, corneal aesthesiometry and in vivo confocal laser-scanning microscopy (CCM). Conjunctival impression cytology was performed in six FD patients and six controls, to assess for expression of two markers of the autophagy-lysosome pathway: the microtubule-associated protein light chain 3 (LC3) and lysosome-associated membrane protein 2 (LAMP2). RESULTS: Cornea verticillata and increased conjunctival vessel tortuosity were detected respectively in 67% and 33% of patients with FD. Compared with healthy subjects, patients affected by FD showed a significant reduction in corneal nerve fiber length, density and nerve branching on CCM and a significantly increased expression of LC3 on conjunctival impression cytology (p < 0.001). No changes were observed in the conjunctival expression of LAMP2 between the two groups. CONCLUSIONS: This study shows that FD is associated with ocular surface alterations including corneal and conjunctival morphology, innervation and vascularization changes. Our data demonstrate an increased expression of LC3 protein in patients with FD, suggesting that alteration of the autophagy-lysosome pathway may play a role in the occurrence of ocular manifestations.

Orbital lesions, an interdisciplinary pathology. The experience of the maxillo-facial surgeons.

AIM: The main focus of this paper was to describe our experience in the management of primary lesions involving the orbit, analyzing signs and symptoms and illustrating surgical management. MATERIAL OF STUDY: We describe our experience managing 62 consecutive patients diagnosed with orbital tumors confined to the orbital content (not involving skin or bone, with no intracranial invasion) and treated between January 2013 and December 2016. Demographic characteristics, symptoms, clinical findings, histological types and approaches have been recorded. RESULTS: We found that the most common clinical manifestations were exophthalmos/proptosis and ocular movement impairment; the most common histological types were vascular malformation and ocular adnexal lymphomas. DISCUSSION: Primary neoplasms involving orbital contents include a broad spectrum of pathologies difficult to manage without a firm diagnosis, usually histological. Different surgical accesses are described in order to perform incisional biopsy or resection of the mass. CONSCLUSION: In every case, accurate surgical planning is mandatory, in order to prevent functional and/or aesthetic complications. KEY WORDS: Blepharoplasty incision, Intraorbital neoplasia, Lateral orbital tumor, Orbitotomy, Surgical treatment, Transconjunctival approach.

Acute Stroke Care in Mexico City: The Hospital Phase of a Stroke Surveillance Study.

Background: Acute stroke care has greatly improved in recent decades. However, the increasing stroke mortality in low-to-middle income countries suggests that progress has not been reached completely by these populations. Here we present the analysis of the hospital phase of the first population-based stroke surveillance study. Methods: A daily hospital surveillance method was used to identify adult patients with acute stroke during 18 months in six hospitals. We abstracted data on demographics, vascular risk factors, neuroimaging-confirmed stroke types, and clinical data. Results: A total of 1361 adults with acute stroke were identified (mean age 69.2 years; 52% women) with transient ischemic attack (5.5%), acute ischemic stroke (68.6%), intracerebral hemorrhage (23.1%), cerebral venous thrombosis (0.2%), and undetermined stroke (2.6%). The main risk factors were hypertension (80.7%) and diabetes mellitus (47.6%). The usage rate of thrombolysis was 3.6%, in spite of the fact that 37.2% of acute ischemic stroke patients arrived in <4.5 h. The 30-day case fatality rate was 32.6%, higher in hemorrhagic than ischemic stroke. Conclusion: We identified limitations in acute stroke care in the Mexico City, including neuroimaging availability and thrombolysis usage. The door-to-door phase will help to depict the acute stroke burden in Mexico.

Understanding Vernal Keratoconjunctivitis: Beyond Allergic Mechanisms.

Vernal keratoconjunctivitis (VKC) is a chronic, recurrent, inflammatory disease of the cornea and conjunctiva mostly affecting boys in prepubertal age. VKC recurrence is characterized by intense symptoms of itching, redness, and photophobia associated with corneal damage, impairment of visual function, and quality of life. The pathogenesis of VKC has not yet been completely understood, and it is still controversial. In fact, VKC is considered an ocular allergic disease due to the involvement of immunoglobulin E, eosinophils, and mast cells, and of a lymphocyte T-helper type 2 reaction. However, approximately half of VKC patients have negative allergological history and testing, suggesting that other pathogenic mechanisms participate in VKC development and severity. Specifically, evidence suggests that genetic, endocrine, neuronal factors and an imbalance of innate immunity are involved in the pathogenesis of VKC. The purpose of this review is to summarize evidence on the pathogenic role of innate immunity, neuroimmune reaction, and hormonal changes in VKC. Increasing understanding of the pathogenic mechanisms behind VKC may lead to the identification of novel biomarkers for diagnosis and/or potential therapeutic targets in order to improve the management of this challenging condition.

Hypoxia-dependent drivers of melanoma progression.

Hypoxia, a condition of low oxygen availability, is a hallmark of tumour microenvironment and promotes cancer progression and resistance to therapy. Many studies reported the essential role of hypoxia in regulating invasiveness, angiogenesis, vasculogenic mimicry and response to therapy in melanoma. Melanoma is an aggressive cancer originating from melanocytes located in the skin (cutaneous melanoma), in the uveal tract of the eye (uveal melanoma) or in mucosal membranes (mucosal melanoma). These three subtypes of melanoma represent distinct neoplasms in terms of biology, epidemiology, aetiology, molecular profile and clinical features.In this review, the latest progress in hypoxia-regulated pathways involved in the development and progression of all melanoma subtypes were discussed. We also summarized current knowledge on preclinical studies with drugs targeting Hypoxia-Inducible Factor-1, angiogenesis or vasculogenic mimicry. Finally, we described available evidence on clinical studies investigating the use of Hypoxia-Inducible Factor-1 inhibitors or antiangiogenic drugs, alone or in combination with other strategies, in metastatic and adjuvant settings of cutaneous, uveal and mucosal melanoma.Hypoxia-Inducible Factor-independent pathways have been also reported to regulate melanoma progression, but this issue is beyond the scope of this review.As evident from the numerous studies discussed in this review, the increasing knowledge of hypoxia-regulated pathways in melanoma progression and the promising results obtained from novel antiangiogenic therapies, could offer new perspectives in clinical practice in order to improve survival outcomes of melanoma patients.