How temperature can alter the combined effects of carbon nanotubes and caffeine in the clam Ruditapes decussatus?

Nowadays, multi-walled carbon nanotubes are considered to be emerging contaminants and their impact in ecosystem has drawn special research attention, while other contaminants, such as caffeine, have more coverage in literature. Despite this, the effects of a combination of the two has yet to be evaluated, especially considering predicted temperature rise. In the present study a typical bioindicator species for marine environment, the clam Ruditapes decussatus, and classical tools, such as biomarkers and histopathological indices, were used to shed light on the species' response to these contaminants, under actual and predicted warming scenarios. The results obtained showed that both contaminants have a harmful effect at tissue level, as shown by higher histopathological index, especially in digestive tubules. Temperatures seemed to induce greater biochemical impacts than caffeine (CAF) and -COOH functionalized multi-walled carbon nanotubes (f-MWCNTs) when acting alone, namely in terms of antioxidant defences and energy reserves content, which were exacerbated when both contaminants were acting in combination (MIX treatment). Overall, the present findings highlight the complex response of clams to both pollutants, evidencing the role of temperature on clams' sensitivity, especially to mixture of pollutants.

Transepithelial iontophoresis corneal collagen cross-linking for progressive keratoconus: initial clinical outcomes.

PURPOSE: To report initial clinical results of transepithelial corneal collagen cross-linking with iontophoresis (I-CXL). METHODS: Twenty eyes of 20 patients diagnosed as having progressive keratoconus who underwent I-CXL were included in this prospective non-randomized clinical study. Corrected distance visual acuity (CDVA), spherical equivalent and cylinder refraction, various corneal topography and Scheimpflug tomography parameters, aberrometry, anterior segment optical coherence tomography, and endothelial cell count were assessed at baseline and at 1, 3, 6, and 12 months postoperatively. RESULTS: CDVA improved significantly at 3, 6, and 12 months postoperatively (logMAR difference of -0.07 ± 0.01, -0.09 ± 0.03, and -0.12 ± 0.06, respectively; P < .05). Aberrometry remained stable during follow-up and a trend toward improvement was noted. All topographic parameters (including maximum keratometry) were stable during the follow-up, but exhibited a positive non-significant trend toward improvement. Minimum corneal thickness values were stable for up to 12 months postoperatively. None of the patients showed a progression of keratoconus. Endothelial cell counts did not change significantly (P > .05). CONCLUSIONS: Preliminary results up to 1 year postoperatively indicate the efficacy of I-CXL in stabilizing the progression of this degenerative disease combined with significant improvement of CDVA. I-CXL, which spares the corneal epithelium, has the potential to become a valid alternative for halting the progression of keratoconus while reducing postoperative patient pain, risk of infection, and treatment time in select patients; however, the relative efficacy of this technique compared to standard epithelium-off techniques remains to be determined.

Expanding the Phenotype of the CACNA1C-Associated Neurological Disorders in Children: Systematic Literature Review and Description of a Novel Mutation.

Background: CACNA1C gene encodes the alpha 1 subunit of the CaV1.2 L-type Ca2+ channel. Pathogenic variants in this gene have been associated with cardiac rhythm disorders such as long QT syndrome, Brugada syndrome and Timothy syndrome. Recent evidence has suggested the possible association between CACNA1C mutations and neurologically-isolated (in absence of cardiac involvement) phenotypes in children, giving birth to a wider spectrum of CACNA1C-related clinical presentations. However, to date, little is known about the variety of both neurological and non-neurological signs/symptoms in the neurologically-predominant phenotypes. Methods and Results: We conducted a systematic review of neurologically-predominant presentations without cardiac conduction defects, associated with CACNA1C mutations. We also reported a novel de novo missense pathogenic variant in the CACNA1C gene of a children patient presenting with constructional, dressing and oro-buccal apraxia associated with behavioral abnormalities, mild intellectual disability, dental anomalies, gingival hyperplasia and mild musculoskeletal defects, without cardiac conduction defects. Conclusions: The present study highlights the importance of considering the investigation of the CACNA1C gene in children's neurological isolated syndromes, and expands the phenotype of the CACNA1C related conditions. In addition, the present study highlights that, even in absence of cardiac conduction defects, nuanced clinical manifestations of the Timothy syndrome (e.g., dental and gingival defects) could be found. These findings suggest the high variable expressivity of the CACNA1C gene and remark that the absence of cardiac involvement should not mislead the diagnosis of a CACNA1C related disorder.

Corneal collagen cross-linking in patients with keratoconus from the Dresden protocol to customized solutions: theoretical basis.

Keratoconus is an ectatic condition characterized by gradual corneal thinning, corneal protrusion, progressive irregular astigmatism, corneal fibrosis, and visual impairment. The therapeutic options regarding improvement of visual function include glasses or soft contact lenses correction for initial stages, gas-permeable rigid contact lenses, scleral lenses, implantation of intrastromal corneal ring or corneal transplants for most advanced stages. In keratoconus cases showing disease progression corneal collagen crosslinking (CXL) has been proven to be an effective, minimally invasive and safe procedure. CXL consists of a photochemical reaction of corneal collagen by riboflavin stimulation with ultraviolet A radiation, resulting in stromal crosslinks formation. The aim of this review is to carry out an examination of CXL methods based on theoretical basis and mathematical models, from the original Dresden protocol to the most recent developments in the technique, reporting the changes proposed in the last 15y and examining the advantages and disadvantages of the various treatment protocols. Finally, the limits of non-standardized methods and the perspectives offered by a customization of the treatment are highlighted.

Compatibility of a New Ocular Surface Dye with Disposable and Bi-Weekly Soft Contact Lenses: An Experimental Study.

Ocular surface staining for assessing corneal and conjunctival epithelium integrity is typically conducted using fluorescein, lissamine green, or rose Bengal dyes. Recently, a novel vital dye, REmark®, based on riboflavin, has been proposed for ocular surface examination. In the management of corneal and ocular surface diseases (OSD), the use of contact lenses is integral to therapeutic strategies. This study explores the compatibility of REmark® with four different types of disposable or bi-weekly soft contact lenses. Morphological variations observed under stereomicroscopy and ultraviolet (UV) ray transmittance in the visible spectrum (VIS) were evaluated at 2 and 4 h post-immersion of the contact lenses in both the original fluid and the new dye. The findings indicate no significant differences between the group treated with the original liquid and those immersed in REmark®, except for a yellow hue observed in the latter group, which dissipates after 8 h in physiological solution. This study highlights the potential of utilizing the new vital dye for ophthalmologic examinations even in the presence of applied soft contact lenses, offering a promising avenue for improved diagnostic practices and patient comfort.

Unilateral proptosis in thyroid eye disease with subsequent contralateral involvement: retrospective follow-up study.

BACKGROUND: The purpose of this retrospective follow-up study is to evaluate the prevalence of patients with thyroid eye disease presenting with apparent unilateral proptosis and determine the occurrence of exophthalmos in contralateral non-proptotic eye over the time. Associated features with this event were evaluated. METHODS: A cohort of 655 consecutive patients affected by thyroid eye disease with a minimum follow-up of 10 years was reviewed. Exophthalmos was assessed by using both Hertel exophthalmometer and computed tomography (CT). The influence of age, gender, hormonal status and of different therapies such as corticosteroids, radiotherapy and surgical decompression on this disease progression was evaluated. RESULTS: A total of 89 patients (13.5%) (95% confidence interval [CI] 15%-10%) had clinical evidence of unilateral exophthalmos at the first visit. Among these, 13 patients (14%) (95% CI 22%-7%) developed subsequent contralateral exophthalmos. The increase of protrusion ranged from 2 to 7 mm (mean of 4.2). The time of onset varied from 6 months to 7 years (mean time: 29 months). Smoking status, young age and surgical decompression are significantly associated with development of contralateral proptosis (p< .05). CONCLUSIONS: Asymmetric thyroid eye disease with the appearance of unilateral exophthalmos at the initial examination is a fairly frequent event, while subsequent contralateral proptosis occurs less commonly. However, physicians should be aware that young patients, particularly if smokers, undergoing orbital decompression in one eye may need further surgery on contralateral side over time.

Corneal Cross-linking for Progressive Keratoconus in Patients Older Than 40 Years: Long-term Follow-up.

PURPOSE: To assess the long-term efficacy and safety of epithelium-off corneal cross-linking according to the standard (Dresden) protocol (S-CXL) in patients with progressive keratoconus older than 40 years. METHODS: Seventy-six eyes of 64 patients with a mean age of 46.4 ± 5.2 years were included. At baseline and after 6, 12, 24, 36, 48, 60, 72, 84, and more than 96 months (when available) after S-CXL, all patients were assessed with distance-corrected visual acuity (DCVA) and corneal topography and tomography with Pentacam HR (OCULUS Optikgeräte GmbH). A generalized linear model was used to compare the groups. Outcome measures were maximum keratometry, thinnest point, coma, spherical, and higher order aberrations, and ABC values. Fixed and random factors were age, gender, atopy, laterality, and group. RESULTS: The mean follow-up time was 62.1 ± 40.1 months (range: 12 to 144 months). The main outcome of the study was the evidence that S-CXL was able to safely stop the progression of keratoconus in all patients with none requiring repeat CXL. The generalized linear model analysis showed no significant change in DCVA over time (P = 1.000), but atopy was negatively associated with DCVA (P = .030, B = -0.69). The generalized linear model also showed that CXL was able to induce a significant flattening demonstrated as reduction of maximum keratometry (P = .001, B = -0.35) and A value (P =.001, B = -0.015) of the ABC display. Similarly, coma aberration was reduced over time (P = .006, B = -0.005). CONCLUSIONS: S-CXL was confirmed to be a safe and effective treatment for progressive keratoconus even after the age of 40 years, inducing a significant flattening of the cone. [J Refract Surg. 2021;37(5):338-342.].

Evaluating keratoconus progression prior to crosslinking: maximum keratometry vs the ABCD grading system.

PURPOSE: To evaluate the correlation between changes in maximum keratometry (Kmax) and ABC values from the ABCD Progression Display (Pentacam) in progressive keratoconus (KC) and to evaluate whether the ABC changes were able to detect progression earlier than Kmax. SETTING: Humanitas Clinical and Research Center, Rozzano, Milan, Italy. DESIGN: Retrospective study. METHODS: Kmax, ABC values, and thinnest point (ThCT) were recorded at the day of corneal crosslinking (CXL) (T0) and previous follow-up (T-1). In patients without earlier progression in Kmax, follow-up examination (T-2) was used to determine whether any of the ABC parameters reached statistical significance for progression. RESULTS: Seventy-six eyes of 63 patients scheduled for CXL with documented progression (Kmax increase of >1.00 diopter) were included. There was a significant, albeit moderate, correlation between the change in Kmax between T0 and T-1 and the change in both A (ρ = 0.391) and B values (ρ = 0.339). There was no significant correlation between the change in Kmax between T0 and T-1 and the change in either C or ThCT. In patients with T-2 examinations, 16 (51.6%) of 31 patients showed a statistically significant change on the ABCD progression display that was not detected with Kmax. CONCLUSIONS: This study showed a significant, but moderate, correlation between the change in Kmax and the change in A and B values in progressive KC. Moreover, more than half of the cases showed documented progression earlier with the ABCD progression display than that detected by standard Kmax changes. This study suggests possible changes in progression criteria to allow for earlier intervention.

Effects of temperature on caffeine and carbon nanotubes co-exposure in Ruditapes philippinarum.

In the marine environment, organisms are exposed to a high and increasing number of different contaminants that can interact among them. In addition, abiotic factors can change the dynamics between contaminants and organisms, thus increasing or even decreasing the toxic effect of a particular compound. In this study, the effects of caffeine (CAF) and functionalized multi-walled carbon nanotubes (f-MWCNTs) induced in the clam Ruditapes philippinarum were evaluated, acting alone and in combination (MIX), under two temperature levels (18 and 21 °C). To assess the impact of such compounds, their interaction and the possible influence of temperature, biochemical and histopathological markers were investigated. The effects of f-MWCNTs and caffeine appear to be clearly negative at the control temperature, with lower protein content in contaminated clams and a significant decrease in their metabolism when both pollutants were acting in combination. Also, at control temperature, clams exposed to pollutants showed increased antioxidant capacity, especially when caffeine was acting alone, although cellular damages were still observed at CAF and f-MWCNTs treatments. Increased biotransformation capacity at 18 °C and MIX treatment may explain lower caffeine concentration observed. At increased temperature differences among treatments were not so evident as at 18 °C, with a similar biological pattern among contaminated and control clams. Higher caffeine accumulation at MIX treatment under warming conditions may result from clams' inefficient biotransformation capacity when exposed to increased temperatures.

Epiphora and unrecognized paranasal sinuses pathology.

PURPOSE: to report five patients all presenting with persistent unilateral epiphora as a sign of unexpected and rare lesions causing Secondary Acquired Nasolacrimal Duct Obstruction (SANDO) and the risks associated to an incomplete diagnostic work-up. OBSERVATIONS: the cases presented are: (1) Fungus ball, (2) Pyogenic granuloma, (3) Sinonasal inverted papilloma (4) Sinonasal inverted papilloma with synchronous squamous cell carcinoma, (5) Squamous cell carcinoma of the lacrimal sac. CONCLUSIONS AND IMPORTANCE: masses are uncommon but not a rare cause of nasolacrimal duct obstruction. Surgical teams performing large numbers of dacryocystorhinostomies should be aware of such pathology and perform a systematic multidisciplinary approach.

Corneal Cross-linking for Progressive Keratoconus: Up to 13 Years of Follow-up.

PURPOSE: To assess the long-term efficacy and safety of epithelium-off corneal cross-linking according to the Dresden protocol (S-CXL) in progressive keratoconus. METHODS: Patients treated with S-CXL from April 2006 to January 2010 at Humanitas Clinical and Research Center, Rozzano, Italy, who completed at least 10 years of follow-up were included. Corrected distance visual acuity (CDVA), refraction, and corneal topography and tomography with Pentacam (OCULUS Optikgeräte GmbH) were evaluated at baseline and 10+ years after the procedure. The definition of progression after S-CXL was two of the following three criteria: increase of "A" value, increase of "B" value, or decrease of minimum thickness evaluated with the ABCD progression display above 95% CI for the post-CXL population. RESULTS: Twenty-seven eyes of 22 patients were included. At a mean of 11 years of follow-up (maximum 13 years), S-CXL was able to maintain CDVA and induce significant regularization of the corneal surface as demonstrated by a significant decrease of the central keratoconus index (P = .035) and a decrease of anterior curvature ("A" value) starting from 2.54 ± 2.46, which reduced to 1.14 ± 1.60 (P = .005) at 10+ years of follow-up. Two of 27 eyes included showed significant progression after S-CXL (7.4%). CONCLUSIONS: S-CXL was confirmed to be a safe and effective treatment for progressive keratoconus with a failure rate of 7.4% at up to 13 years of follow-up. The authors suggest the use of a combined progression system that evaluates anterior and posterior curvature and with thickness map together with the knowledge of the noise level of the testing system. [J Refract Surg. 2020;36(12):838-843.].

Ocular Onset of Paraneoplastic Pemphigus Presenting as Hyperemic Conjunctivitis and Massive Bilateral Eyelid Ulceration: A Case Report and Literature Review.

INTRODUCTION: Paraneoplastic clinical signs are characterized by a large and heterogeneous variety of manifestations due to several possible underlying neoplasms. Paraneoplastic pemphigus (PNP) is a particular paraneoplastic variety that usually primarily affects the dermic and/or oral mucosa and is characterized by a high rate of mortality (90%). Therefore, it is important to recognize its possible signs early. This report describes a case of ocular paraneoplastic pemphigus (PNP) presenting with recalcitrant eyelid ulceration and hyperemic conjunctivitis caused by an undiagnosed prostate cancer. METHODS: A 77-year-old man was admitted to our department because of recalcitrant hyperemic conjunctivitis in both eyes, complicated with large ulceration of both upper eyelids in spite of topical therapy. After 3 weeks, oral mucositis and bullous dermatitis on the chest and arms developed. RESULTS: Complete slit lamp ocular study, conjunctival swabs, routine hematologic tests, serum neoplasm markers, indirect immunofluorescence study, immunoblotting, and oral mucose biopsy with direct immunofluorescence were performed under the hypothesis of a paraneoplastic sign. Total body computed tomography scan and ultrasound-guided needle prostate biopsy completed the diagnostic process and confirmed the diagnosis of prostate PNP. Complete remission of ocular clinical signs was achieved by treatment of the prostate malignancy with systemic immunosuppressive therapy and chemotherapy.

Long-Term Follow-Up after Intravenous Immunoglobulin Therapy in Patients with Severe Ocular Mucous Membrane Pemphigoid Unresponsive to Conventional Therapy.

Mucous membrane pemphigoid (MMP) is a heterogeneous group of rare, systemic, autoimmune subepidermal inflammatory disease that affects mucous membranes and the eye. In its most severe forms, this disease needs systemic therapy, usually based on steroids and immunosuppressant agents. In unresponsive cases or in the presence of contraindications or severe side effects due to conventional systemic corticosteroid and/or immunosuppressant therapy, a therapy shift to high-dose intravenous immunoglobulins (IVIg) has been recommended in other reports. This new therapy has proven to be effective in stopping ocular pemphigoid, but the data regarding the long-term effect on the disease activity or reactivation are extremely scarce, so the novel scientific aim of this study was to evaluate the clinical outcomes after a 9-year follow-up in 12 eyes (6 patients) affected by MMP with ocular involvement, successfully treated with IVIg therapy, as previously described in our report published in 2008. The evaluation of ocular and extraocular disease progression was performed at the end of IVIg therapy and at the end of the follow-up period. After 9 years, all the eyes enrolled showed a long-lasting remission of ocular and oral symptoms with a significant steroid-sparing effect. In conclusion, the IVIg has to be considered as a safe and successful alternative therapy in patients with severe ocular mucous membrane pemphigoid; furthermore, this kind of therapy seems to be effective in maintaining the clinical remission by the time.

Paraneoplastic syndrome--unresponsive systemic hypertension and fever as expression of primitive ciliary body carcinoma in a blind painful eye: a case report.

BACKGROUND: The purpose of this study was to present a case of paraneoplastic systemic hypertension and fever in an undiagnosed primary ciliary body carcinoma arising in a painful blind eye. CASE PRESENTATION: A 37-year-old white man with a history of blindness since childhood was enucleated for neovascular glaucoma because of intractable pain in his right eye. A histopathological examination revealed a ciliary body carcinoma. One year later, an invasive recurrence of his orbit and ethmoid was detected and a debulking procedure was performed. He had untreatable fever and multidrug-resistant systemic hypertension for 3 months before the neoplasm diagnosis. He recovered from fever and systemic hypertension only after tumor excision and relapsed 1 year later when synchronous tumor dissemination was shown through a computed tomography scan. Tumor metastases, despite surgery and chemotherapy, caused his death. CONCLUSIONS: Paraneoplastic symptoms such as fever and hypertension may be due to unrecognized ocular malignancy. This case report intends to emphasize the importance of histopathological examination of an enucleated phthisical painful blind eye.

Transepithelial Iontophoresis Versus Standard Corneal Collagen Cross-linking: 1-Year Results of a Prospective Clinical Study.

PURPOSE: To compare 1-year transepithelial corneal collagen cross-linking with iontophoresis (I-CXL) outcomes with standard CXL (S-CXL) epithelium-off for progressive keratoconus. METHODS: Forty eyes of 40 patients with progressive keratoconus were included in this comparative, prospective clinical study. Corrected distance visual acuity (CDVA), spherical equivalent, cylinder refraction, corneal topography, Scheimpflug tomography, aberrometry, and endothelial cell count were assessed at baseline and at 1, 3, 6, and 12 months of follow-up. RESULTS: Patients received either I-CXL (20 eyes) or S-CXL (20 eyes). Functional parameters (visual acuity and aberrometry) showed a significant improvement (P < .05) after 6 and 12 months of follow-up in both groups. In the I-CXL group, the CDVA showed a rapid recovery of vision after 3 months (P = .01) compared to baseline. Morphological parameters showed a significant reduction of maximum keratometry in the S-CXL group by -1.05 ± 1.51 diopters (D) after 12 months, whereas the I-CXL group curvature was stable (-0.31 ± 1.87 D). Minimum pachymetry values were stable even after 12 months of follow-up in the I-CXL group, whereas a significant corneal thinning 12 months following treatment was recorded in the S-CXL group (P < .001). None of the patients had continuous progression of keratoconus or had to repeat CXL procedures. Endothelial cell counts did not change significantly (P > .05). CONCLUSIONS: The 1-year outcomes suggest that I-CXL might be comparable to S-CXL in stabilizing the progression of the degenerative ectatic disease. Additionally, quicker improvement of functional parameters was reported in the I-CXL group. [J Refract Surg. 2016;32(10):672-678.].