Skin rejuvenation effect of the combined PDLLA and non cross-linked hyaluronic acid: A preliminary study.

BACKGROUND: Skin aging is characterized by wrinkles, rough skin texture, pigmentation, facial erythema, and telangiectasia through structural and functional changes in the epidermis and dermis. Recently, injectable poly(D, L-lactic acid), a biodegradable polymer, has been used widely for skin rejuvenation. AIMS: This study aims to assess the efficacy and safety of injectable dermal poly D, L-lactic acid) for skin rejuvenation. PATIENTS/METHODS: A total of 16 patients who desired skin rejuvenation were included. All participants received two or three procedure sessions with a 4 weeks interval between sessions. Clinical and three-dimensional images at baseline, before each procedural session, and follow-up visits were obtained. Therapeutic effects were assessed by evaluating signs of aging skin and overall improvement by dermatologists and patients. Histologic examinations with special stains were performed on the posterior auricular areas of consenting patients at baseline and follow-up visits after injecting poly D L-lactic acid into the postauricular area as in the face. RESULTS: Overall, statistically significant differences were observed in all signs of aging skin, such as fine wrinkles, skin texture, irregular pigmentation, telangiectasia, and facial erythema before and after treatments. Half (50%) of patients responded that there was more than 50% overall improvement. There were no severe adverse events. Histologic examination demonstrated increases in collagen and elastic fibers in the dermis. CONCLUSIONS: Results of this preliminary study suggest that injectable dermal poly D, L-lactic acid can significantly affect skin rejuvenation without causing any serious adverse events.

Examining the efficacy of verteporfin photo-dynamic therapy (PDT) at different dose & fluence levels.

OBJECTIVES: Photodynamic therapy (PDT) is a vaso-occlusive treatment for a number of chorioretinal vascular pathologies. We aimed to retrospectively analyse efficiency and safety of PDT for different conditions (central serous retinopathy (CSR), age-related macular degeneration (AMD), macular telangiectasia type 2 and choroidal hemangioma) and with different verteporfin parameters. METHODS: Clinical parameters were ascertained from the medical records of patients undergoing PDT over a 6-year period. This included indications for PDT, dosing regimens of verteporfin PDT (which includes treatment dose of verteporfin and fluence). Response to treatment was measured by best corrected visual acuity (BCVA) and central foveal thickness (CFT) on ocular coherence tomography. Complications and side effects were recorded. RESULTS: 67.4 % (31/46) of PDT treatments performed over the last six years were for CSR. In the CSR cohort, there were significant improvements in BCVA (0.47 ± 0.24 to 0.29 ± 0.27, p < 0.05) and CFT (350.2µm ± 66.9 µm to 286.1µm ± 60.6 µm. In the AMD cohort, there was no change in BCVA (1.08 ± 0.52 to 1.07 ± 0.53, p = 0.96) but significant improvement in CFT (488.2µm ± 164.6 µm to 348.7µm ± 65.7 µm, p < 0.05). There was no significant difference in BCVA or CFT for macular telangiectasia type 2 and choroidal hemangioma. CONCLUSIONS: PDT continues to have a role in the management of medical retina conditions. Our results show PDT is most effective in improving and stabilizing visual acuity in CSR, with earlier intervention resulting in better outcomes.

Low concentration of sodium tetradecyl sulfate and hypertonic glucose solution for the treatment of telangiectasia: A prospective randomized clinical trial.

OBJECTIVES: This study aimed to compare telangiectasias disappearance after sclerotherapy with hypertonic glucose (HG) and different concentrations of sodium tetradecyl sulfate (STS). METHODS: Women aged 18-70 years with telangiectasias were included. The primary efficacy endpoint was telangiectasia disappearance. The clearing of vessels was assessed using a six-point scale (from 0 to 5). RESULTS: A total of 116 women completed an 8-week follow-up: 31, 27, 25, and 33 were in the HG 75%, STS 0.05%, STS 0.1%, and STS 0.15% groups, respectively. The median score of vein disappearance was significantly lower in the STS 0.05% (3, 0.25-4), STS 0.1% (3, 1.25-4), and STS 0.15% (4, 2-4) groups than in the HG group (4, 3-5) after 56 days, p = .00002. CONCLUSION: Sclerotherapy of telangiectasias with 75% HG showed significantly better results than low concentrations of STS. TRIAL REGISTRATION: ClinicalTrials.gov NCT04132323.

Rosacea management: A comprehensive review.

Rosacea is a chronic cutaneous disorder affecting primarily the face, characterized by erythema, transient or persistent, telangiectasia, and inflammatory lesions including papulo-pustules and swelling. The essential component of the disease is the persistent erythema of facial skin. Episodes of flushing (acute-subacute intermittent vasodilation) are common. Swelling and erythema of the nose along with dilatation of the pilosebaceous poral orifices, known as rhinophyma, can be noted in chronic cases. Rosacea affects up to 10% of the world population and is especially noted in fair-skinned individuals aged 35-50. Women are affected more often than men. Several treatment modalities including topical medications, systemic drugs, lasers, and light-based therapies have been used for the management of rosacea with variable results. Topical medications such as azelaic acid, metronidazole, and sulfacetamide/sulfur, oral antibiotics such as tetracyclines, and oral retinoids alone or, most commonly, in combination form the mainstay of treatment. Light therapies such as intense pulsed light and pulsed dye laser are best used for the erythemato-telangiectatic type. Topical brimonidine, oxymetazoline, ivermectin, tacrolimus, pimecrolimus, low-dose modified-release tetracyclines and botulinum toxin are the new additions to the therapeutic armamentarium. This article provides a comprehensive review of the various therapies used for rosacea.

Ado-trastuzumab emtansine associated spider telangiectasia.

INTRODUCTION: Breast cancer is the most common cancer in women. Human epidermal growth factor receptor 2 (HER2) positivity rate is 20% and generally has a poor prognosis. Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate consisting of HER2 target monoclonal antibody trastuzumab and microtubule inhibitor emtansine. The most common side effects are fatigue, diarrhea, anemia, and it is generally a safe and tolerable agent. CASE REPORT: In our case, we reported our patient who developed mucosal and cutaneous telangiectasia after T-DM1 treatment and who had a complete response in metastases after skin lesions. MANAGEMENT AND OUTCOME: While no side effects were observed during the use of T-DM1 for HER2 positive disease, nose bleeding and spider telangiectasia on the skin developed in the 9th month of the treatment. In these lesions, which did not require any treatment, no regression was observed during T-DM1 treatment. DISCUSSION: We think that T-DM1, which was detected with a low incidence of skin toxicity in studies, may form telangiectatic lesions due to vascular dilatation through emtansine, and therefore care should be taken in the treatment of T-DM1.

Clinical and neuroimaging findings in 33 patients with MCAP syndrome: A survey to evaluate relevant endpoints for future clinical trials.

Megalencephaly-CApillary malformation-Polymicrogyria (MCAP) syndrome results from somatic mosaic gain-of-function variants in PIK3CA. Main features are macrocephaly, somatic overgrowth, cutaneous vascular malformations, connective tissue dysplasia, neurodevelopmental delay, and brain anomalies. The objectives of this study were to describe the clinical and radiological features of MCAP, to suggest relevant clinical endpoints applicable in future trials of targeted drug therapy. Based on a French collaboration, we collected clinical features of 33 patients (21 females, 12 males, median age of 9.9 years) with MCAP carrying mosaic PIK3CA pathogenic variants. MRI images were reviewed for 21 patients. The main clinical features reported were macrocephaly at birth (20/31), postnatal macrocephaly (31/32), body/facial asymmetry (21/33), cutaneous capillary malformations (naevus flammeus 28/33, cutis marmorata 17/33). Intellectual disability was present in 15 patients. Among the MRI images reviewed, the neuroimaging findings were megalencephaly (20/21), thickening of corpus callosum (16/21), Chiari malformation (12/21), ventriculomegaly/hydrocephaly (10/21), cerebral asymmetry (6/21) and polymicrogyria (2/21). This study confirms the main known clinical features that defines MCAP syndrome. Taking into account the phenotypic heterogeneity in MCAP patients, in the context of emerging clinical trials, we suggest that patients should be evaluated based on the main neurocognitive expression on each patient.

Therapeutic Opportunities for Intestinal Angioectasia- Targeting PPARγ and Oxidative Stress.

Recurrent and acute bleeding from intestinal tract angioectasia (AEC) presents a major challenge for clinical intervention. Current treatments are empiric, with frequent poor clinical outcomes. Improvements in understanding the pathophysiology of these lesions will help guide treatment. Using data from the US Food and Drug Administration (FDA)'s Adverse Event Reporting System (FAERS), we analyzed 12 million patient reports to identify drugs inversely correlated with gastrointestinal bleeding and potentially limiting AEC severity. FAERS analysis revealed that drugs used in patients with diabetes and those targeting PPARγ-related mechanisms were associated with decreased AEC phenotypes (P < 0.0001). Electronic health records (EHRs) at University of Cincinnati Hospital were analyzed to validate FAERS analysis. EHR data showed a 5.6% decrease in risk of AEC and associated phenotypes in patients on PPARγ agonists. Murine knockout models of AEC phenotypes were used to construct a gene-regulatory network of candidate drug targets and pathways, which revealed that wound healing, vasculature development and regulation of oxidative stress were impacted in AEC pathophysiology. Human colonic tissue was examined for expression differences across key pathway proteins, PPARγ, HIF1α, VEGF, and TGFß1. In vitro analysis of human AEC tissues showed lower expression of PPARγ and TGFß1 compared with controls (0.55 ± 0.07 and 0.49 ± 0.05). National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) RNA-Seq data was analyzed to substantiate human tissue findings. This integrative discovery approach showing altered expression of key genes involved in oxidative stress and injury repair mechanisms presents novel insight into AEC etiology, which will improve targeted mechanistic studies and more optimal medical therapy for AEC.

Polidocanol Plus Glucose Versus Glucose Alone for the Treatment of Telangiectasias: Triple Blind, Randomised Controlled Trial (PG3T).

OBJECTIVE: The aim of this study was to compare the effectiveness and safety of two sclerosing agents used to treat telangiectasias in the lower limbs: 0.2% polidocanol + 70% hypertonic glucose (HG) vs. 75% HG alone. METHODS: A prospective, randomised, triple blind, controlled, parallel group trial with patients randomly assigned in a 1:1 ratio between January and December 2015, with a two month follow up, from a single academic medical centre in Brazil, was carried out. Participants were women aged 18-65 years with telangiectasias on the lateral aspect of one thigh, classified as C1EpAsPn who underwent sclerotherapy in a single session with 0.2% polidocanol + 70% HG or 75% HG alone to treat the telangiectasias on an area limited by a rectangular template. The primary effectiveness endpoint was elimination of 75% of the telangiectasias within 60 days vs. the pre-treatment pattern. The length of vessels was measured on images obtained before and after treatment using ImageJ software. Safety outcomes were analysed immediately, 7 days, and 60 days after the treatment, and included pigmentation. RESULTS: A total of 115 patients were included, 98 of whom completed the study. Sclerotherapy with 0.2% polidocanol + 70% HG was significantly more effective than with 75% HG alone to treat telangiectasias in the target area (82.2% vs. 63.9%; p < .001); considering a minimum improvement of 75%, there was a 0.49 risk reduction (95% confidence interval 0.24-0.98; p = .047). No severe adverse events occurred in either group. Pigmentation was the most common minor adverse event and was significantly shorter in length in the group treated with 0.2% polidocanol + 70% HG (median 0 cm vs. 0.5 cm, respectively; p = .033). CONCLUSION: Polidocanol 0.2% plus 70% HG had better results than 75% HG alone in sclerosing telangiectasias. No severe adverse events occurred. Pigmentation occurred in both groups and was shorter in length in the group treated with 0.2% polidocanol + 70% HG.

Real-world outcomes of intravitreal anti-vascular endothelial growth factor monotherapy in proliferative type 2 macular telangiectasia.

BACKGROUND: To study the effect of anti-VEGFs in proliferative MacTel 2 METHODS: Sixty-four eyes of 51 patients of MacTel 2 with subretinal neovascular membrane (SRNVM) undergoing intravitreal anti-VEGF monotherapy at our institution between January 2015 and December 2018 were evaluated for visual acuity, central macular thickness (CMT) and total macular volume (TMV) using optical coherence tomography (OCT). Repeat investigations were performed at the final follow-up. RESULTS: Location of SRNVM was foveal (F) in 65.6% eyes and extrafoveal (EF) in 34.4% eyes. Both CMT and TMV were lower significantly at baseline in EF-SRNVM. Fifty-six eyes received intravitreal bevacizumab and 8 eyes received ranibizumab. Average 2.14 ± 1.21 injections (range, 1-6) were administered. After a mean follow-up duration of 16.01 ± 12.96 months, the final visual acuity (VA) improved in 35.9% eyes, reduced in 28.1% and remained unchanged in 35.9% eyes. Significant improvement of VA was seen in F-SRNVM; however, overall, there was no significant improvement in visual acuity. Significant reduction in CMT was seen in F-SRNVM from 391.73 ± 152.45 µm to 293.33 ± 114.77 µm (p < 0.05) while EF-SRNVM did not show significant reduction. Total macular volume overall changed significantly from 8.79 ± 1.69 to 8.05 ± 1.27 (p < 0.05) and individually in F- and EF-SRNVM (p < 0.05). Intravitreal bevacizumab and ranibizumab monotherapy both had similar efficacy. CONCLUSIONS: Anti-VEGF agents can be successfully used to treat proliferative MacTels. Macular volume measurement on OCT may be a useful parameter for evaluating EF-SRNVM and as a prognostic marker of management outcomes.

The First Case of TEMPI Syndrome in Japan.

TEMPI syndrome, a disease entity comprising telangiectasia, erythrocytosis with high erythropoietin, monoclonal gammopathy, perinephric fluid collection, and intrapulmonary shunting, was first described by Sykes et al. in 2011. To our knowledge, only 15 cases have been reported worldwide, none of which were in Japan. We herein report a 47-year-old man who had intractable ascites for 2 and a half years and was referred to our department for a peritoneovenous shunt. In addition to ascites, he had telangiectasia, high erythropoietin, monoclonal gammopathy, and perinephric fluid collection. Thus, this is the first case of TEMPI syndrome in Japan.

Comparison of anatomical and visual outcomes following different anti-vascular endothelial growth factor treatments in subretinal neovascular membrane secondary to type 2 proliferative macular telangiectasia.

PURPOSE: To evaluate central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and visual outcomes following different intravitreal anti-vascular endothelial growth factor (VEGF) treatments in eyes with subretinal neovascular membrane (SRNVM) due to type 2 proliferative macular telangiectasia (Mac Tel 2). MATERIALS AND METHODS: A total of 38 eyes of 34 patients who underwent intravitreal aflibercept (IVA), intravitreal ranibizumab (IVR), or intravitreal bevacizumab (IVB) injections secondary to SRNVM due to type 2 proliferative MacTel were retrospectively reviewed. The CMT, central macular volume (CMV), best corrected visual acuity (BCVA), and SFCT were evaluated at baseline and at 2 weeks, at 1 month, and at final visits following treatment. Spectral-domain optical coherence tomography and enhanced depth optical coherence tomography were used for the analysis. RESULTS: The mean age of the patients was 58.34 ± 12.48 years (range, 27-79 years). The mean follow-up time was 15.97 ± 6.79 months (range 5-32 months). The mean BCVA showed a statistically significant increase in each group (< 0.001). There was no statistically significant difference in BCVA changes between groups in follow-up periods. There was a significant decrease in CMT following IVA (326.4 ± 168.03 µm to 236 ± 58.33 µm) and IVB (383.71 ± 156.79 µm to 343.85 ± 146.25 µm) (p < 0.001, p = 0.004, respectively) whereas no significant decrease in CMT was observed following IVR (374.57 ± 124.28 µm to 339.71 ± 126.10 µm) (p = 0.65) between baseline and final visit. The SFCT significantly decreased following both IVB and IVR treatments (p = 0.009, p = 0.03, respectively). CONCLUSIONS: The IVA, IVR, and IVB were found to be effective with regards to anatomical and visual outcomes in proliferative Mac Tel type 2 patients related with SRNVM. Patients receiving both IVA and IVB needed less injections compared to patients who received IVR. Moreover, IVB and IVR lead to significant decrease in SFCT whereas IVA did not show significant effect on SFCT.

Uso de tartarato de brimonidina para resolução de matting telangiectásico: relato de caso / Use of brimonidine tartrate to resolve telangiectatic matting: case report

Resumo A escleroterapia é, atualmente, o tratamento de escolha para telangiectasias e veias reticulares, apresentando nível de recomendação 1ª pela diretriz europeia para escleroterapia. Os efeitos colaterais mais comuns desse procedimento são a hiperpigmentação e o matting telangiectásico, sendo este último um dos mais temidos em virtude do dano estético e da dificuldade de tratamento. O matting se refere a vasos com diâmetro inferior a 0,2 mm que podem surgir esporadicamente ou em áreas bem definidas, principalmente nos membros inferiores. Este relato apresenta um caso de matting tratado com o uso de tartarato de brimonidina tópico.

Abstract Sclerotherapy is currently the treatment of choice for telangiectasias and reticular veins, with grade 1A recommendation in the European Guideline for sclerotherapy. The most common side effects of this procedure are hyperpigmentation and telangiectatic matting, the second of which provokes great concern because of the esthetic damage and the difficulty of treatment. Matting refers to vessels with a diameter of less than 0.2 mm, which may emerge irregularly or in well-defined areas, especially on the lower limbs. This report presents a case of matting treated with topical Brimonidine Tartrate.

R-propranolol is a small molecule inhibitor of the SOX18 transcription factor in a rare vascular syndrome and hemangioma.

Propranolol is an approved non-selective ß-adrenergic blocker that is first line therapy for infantile hemangioma. Despite the clinical benefit of propranolol therapy in hemangioma, the mechanistic understanding of what drives this outcome is limited. Here, we report successful treatment of pericardial edema with propranolol in a patient with Hypotrichosis-Lymphedema-Telangiectasia and Renal (HLTRS) syndrome, caused by a mutation in SOX18. Using a mouse pre-clinical model of HLTRS, we show that propranolol treatment rescues its corneal neo-vascularisation phenotype. Dissection of the molecular mechanism identified the R(+)-propranolol enantiomer as a small molecule inhibitor of the SOX18 transcription factor, independent of any anti-adrenergic effect. Lastly, in a patient-derived in vitro model of infantile hemangioma and pre-clinical model of HLTRS we demonstrate the therapeutic potential of the R(+) enantiomer. Our work emphasizes the importance of SOX18 etiological role in vascular neoplasms, and suggests R(+)-propranolol repurposing to numerous indications ranging from vascular diseases to metastatic cancer.

Evaluation of selected skin parameters following the application of 5% vitamin C concentrate.

BACKGROUND: Ascorbic acid is a substance with confirmed anti-free-radical properties. It triggers the collagen synthesis, has a depigmenting effect and seals blood vessels. All these properties have a significant effect of the skin's appearance. The characteristic traits of capillary skin include telangiectasias as well as erythema, which might consolidate in the future, along with the feeling of burning and increased skin sensitivity. OBJECTIVES: Study and evaluation of selected parameters of capillary skin after the application of 5% vitamin C concentrate throughout the period of 6 weeks with the use of instrumental tests and questionnaires. METHODS: The research was conducted on a group of 30 women ranging from 30 to 60 years of age with capillary skin indicating visible signs of erythematous plaques. The concentrate was applied once a day. Analyses of skin conditions were conducted four times: before the launch of the research D(0), after two 2D(14), after four 4D(28), and after 6 D(42) weeks of application. The research was conducted with the use of Mexameter MPA equipment, which was used to measure changes in the intensity of erythematous plaques. The depth of wrinkles was measured by PRIMOS system (two times D0 and 6D(42). The research also used VISIA system which allowed to perform visual and numeral skin analyses. Each research was finalized with a questionnaire which provided a subjective evaluation of the examined product among participants. RESULTS: Significant reduction in erythema has been widely recorded. After 2 weeks, erythema dropped by 9%. After 4 weeks, it decreased by 16% and by 21% after 6 weeks. The concentrate's efficiency in diminishing erythematous plaques was confirmed by photographs generated by VISIA photograph system. Thanks to PRIMOS, decrease in both depth and volume of nasolabial folds was recorded in 87% of participants after 6 weeks of research. CONCLUSION: 5% vitamin C concentrate is effective in treating capillary and photograph-aging skin. It decreases erythema and telangiectasias as well as triggers the shallowing of skin wrinkles.

PDT and BF-200 ALA: The therapy option for the treatment of Poikiloderma of Civatte.

Poikiloderma is a chronic skin condition affecting middle-age men and women that comprises cutaneous atrophy, telangiectasias, and changes in the pigmentation of the skin usually of mottled appearance (both hyper- and hypopigmentation). There is no specific medical treatment for Poikiloderma of Civatte (PC), but the use of photoprotector/sunscreen + SPF 50 to avoid prolonged sun exposure is highly recommended in these patients. Some authors recommend the use of topical corticoids in early stages; however, the results have not been satisfactory. Multiple topical (retinoids, dimethyl sulfoxide, or calcineurin inhibitors), systemic (cyclophosphamide), and physical (dermabrasion, phototherapy, and fractional photothermolysis) treatments have been described with unequal and inconsistent responses or unsatisfactory. This report underlies the combination of BF-200 ALA and photodynamic therapy (PDT) with positive results at the clinical level: significant improvement of pigmentary changes and telangiectasias after two PDT sessions.

Inhibitory effect of timolol on topical glucocorticoid­induced skin telangiectasia.

The aim of the present study wasto investigate the potential inhibitory effect of timolol on topical glucocorticoid­induced skin telangiectasia. In rabbits, flumethasone ointment was used to induce skin telangiectasia in the inner ear. Subsequently, timolol maleate (0.5%) eye drops (TMEDs) were administered twice daily for 4 weeks. Expression of the antibacterial peptides 37­amino acid peptide (LL­37) and kallikrein­5 (KLK5) was detected using quantitative polymerase chain reaction (PCR) and semi­quantitative reverse transcription­PCR. In patients with facial skin telangiectasia, one cheek of each patient was assigned to a treatment group and the other to a control group. For the treatment group cheeks, topical application of TMEDs was combined with 0.1% tacrolimus ointment once or twice daily for 8 weeks. The control group cheeks were administered with 0.1% tacrolimus ointment alone. Alterations in lesions were recorded by dermoscopy, and the L, a and b values of lesions were measured, based on the Commission Internationale de l'Éclairage system, with a chromameter prior to and at 1, 2, 4 and 8 weeks following treatment. The results indicated that erythema, papules and telangiectasia were significantly diminished following 4 weeks of treatment with TMEDs in rabbits. Notably, the expression of LL­37 and KLK5 mRNA was increased in the negative control group; however, it was decreased in the trial and blank groups. Clinical and dermoscopy images demonstrated that erythema was reduced in the 2 groups for 1 week, and that telangiectasia in the treatment group was markedly reduced compared with the control group at 4 weeks. The difference of the L and a values of lesions between the treatment and control group was significant (P<0.05). Overall, the present results suggested that the abnormal expression of LL­37 may be one of the mechanisms underlying the pathogenesis of facial corticosteroid addiction dermatitis (FCAD) and TMEDs may inhibit the mRNA expression of LL­37 by downregulating KLK5; in this regard, TMEDs may serve a role in attenuating telangiectasia, which may be beneficial in improving the telangiectasia symptoms of FCAD.