Impact of Upadacitinib on Atopic Keratoconjunctivitis Exacerbated by Dupilumab Treatment in Atopic Dermatitis Patients: A Prospective Dermatological and Ophthalmological Clinical Evaluation in Common Clinical Practice.

Introduction: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin condition with a substantial impact on patients, particularly due to ocular involvement known as atopic keratoconjunctivitis (AKC). Current therapeutic approaches, such as dupilumab, often lead to conjunctivitis, prompting exploration of alternative treatments like upadacitinib. Methods: We collected dermatological and ophthalmological prospective clinical evaluations of six adults with moderate-to-severe AD, undergoing treatment with upadacitinib after discontinuation of dupilumab due to the onset of AKC during therapy and the worsening of dermatitis in particular in the head and neck region. Clinical evaluations, including EASI scores, itch and sleep NRS, DLQI, and ocular parameters, were performed at baseline (during screening assessment before switching to upadacitinib) and then at week 12 and week 24. Clinical evaluation of AKC was performed by a team of ophthalmologists. Results: Upadacitinib not only improved atopic dermatitis in terms of EASI, itching, and sleep NRS, but also demonstrated a notable reduction in ocular signs and symptoms, as indicated by the Visual Analogue Scale (VAS), the Efron scale, and the Ocular Surface Disease Index Symptom Severity (OSDISS) scores. Discussion: Our observation of common clinical practice underscores the substantial impact of biological and small-molecule therapies on AD, emphasizing the limitation posed by dupilumab-associated conjunctivitis. Switching to upadacitinib significantly improved both clinical and functional ocular outcomes, suggesting its potential as an alternative therapeutic option for AD patients with ocular involvement. Conclusion: The presented data provides insights into the complex interplay between systemic therapies and ocular manifestations in AD. Upadacitinib emerges as a promising option to address dupilumab-associated conjunctivitis, offering improved quality of life for patients.

Dupilumab-associated ocular surface disease or atopic keratoconjunctivitis not improved by dupilumab? Upadacitinib may clarify the dilemma: A case report.

Dupilumab-associated ocular surface disease is a common clinical sign appearing in patients with atopic dermatitis (AD) just few months after dupilumab treatment start, developing in about 25% of patients. Atopic keratoconjunctivitis (AKC) is a well-identified clinical entity, defined as a chronic inflammatory disease of eye that affects 25%-40% of patients with AD. Most clinical signs of ocular involvement in AD patients treated with dupilumab overlaps the AKC symptoms and signs. We supposed that Dupilumab-associated ocular surface disease and AKC represent the same disease but differently called by dermatologists and ophthalmologists. AKC-like disease may develop during dupilumab therapy as a consequence of alternative cytokines pathway activation (e.g. IL33) secondary to IL-4/13 pathway block. The novel upadacitinib drug may bypass ILs pathway through Janus Kinases selective inhibition, avoiding positive or negative ILs feedback at the ocular surface level. In this case report, molecular analysis on conjunctival samples showed a lower ocular surface inflammation (lower expression of HLADR) although higher levels of IL4 and IL13 in a patient with AD and AKC during upadacitinib therapy, compared to prior dupilumab treatment. Target therapies in patients suffering from AD may prevent ocular and dermatological comorbidities improving quality of life before quality of skin and vision.

A Functional and Immunologic Point of View on Corneal Endothelial Transplantation: A Systematic Review and Meta-Analysis.

Background: To systematically review and meta-analyze the immunologic aspects and outcomes of various endothelial keratoplasty (EK) techniques, specifically comparing Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK), Ultra-Thin Descemet's Stripping Automated Endothelial Keratoplasty (UT-DSAEK), and Descemet's Membrane Endothelial Keratoplasty (DMEK). Methods: Systematic review and meta-analysis. Main outcomes were the proportion of patients achieving a best spectacle-corrected visual acuity (BSCVA) of 20/20 at 6 months after keratoplasty, rejection rate one year after surgery, BSCVA at last follow up, and postoperative immunomodulating regimen. Results: A higher proportion of DMEK patients achieved a BSCVA of 20/20 after 6 months. UT-DSAEK and DMEK showed similar rejection rates with a lower risk of re-bubbling for UT-DSAEK (4% vs. 20%). Conclusions: DMEK showed faster visual recovery than UT-DSAEK but a similar rejection rate and long-term visual acuity. One-year postoperative slow tapering steroid regimen has a positive but not (yet) significant effect on rejection risk and visual outcomes.

Prophylactic Therapy for Long-Term Ocular Discomfort After Cataract Surgery.

PURPOSE: The cataract surgery dissatisfaction rate is 20% to 35% due to ocular surface discomfort. We investigate the ocular surface discomfort after surgical failure as a consequence of age-related parainflammation. We also aim to prevent it by immune-modulating prophylactic management. METHODS: Monocentric clinical trial realized in a teaching hospital. Prospective, randomized, open-label, unmasked clinical trial. One hundred patients diagnosed with cataracts underwent phacoemulsification surgery. Groups A (<65 years; n = 25) and B (>75 years; n = 25) received surgery only. Groups C and D (both >75 years and both n = 25) used cyclosporine A 0.1% cationic emulsion (CE) eye drops or CE lubricating eye drops (both twice daily), respectively, for 30 days before surgery. Patients were followed up 90 days after surgery. The primary outcome was postoperative ocular surface failure; secondary outcomes examined the influence of prophylactic cyclosporine A 0.1% CE therapy on ocular surface outcomes. RESULTS: Group B demonstrated greater severity regarding ocular surface signs and symptoms throughout the study period, versus all other groups. Signs/symptoms were typically lower in Group A. Group C achieved significant reductions in conjunctival Symptom Assessment in Dry Eye values ( P < 0.05), conjunctival hyperemia severity ( P < 0.01), and meibomian gland dysfunction ( P < 0.001) at Day 45, versus Group B, and tear break-up time was increased ( P < 0.001). Ocular surface inflammatory marker transcription (HLADR, intercellular adhesion molecule 1 [ICAM-1], and interleukin 6 [IL-6]) was significantly downregulated in Group C, versus Group B, at 90 days ( P < 0.05). CONCLUSIONS: Cataract surgery induced ocular surface system failure with a clinically significant persistent inflammatory status (InflammAging) in patients older than 75 years. Prophylactic cyclosporine A 0.1% CE eye drops were associated with improved ocular surface homeostasis and reductions in inflammatory markers.

Ocular Surface Failure in Urban Syndrome.

BACKGROUND: Nowadays, the continuous increase in air pollution has significantly changed air quality, leading to the onset of the so-called urban syndrome (US), an allergic-like conjunctivitis triggered by pollutants. These patients are characterized by persistent dysregulation of ocular surface para-inflammation, causing chronic low-grade inflammation and ocular discomfort, with significant consequences for occupational health and job productivity prospects. This study aims to investigate the effects of topical glycerophosphoinositol (GPI) eye drops on the signs and symptoms of US. METHODS: A multicenter prospective open interventional study was performed. Patients affected by US, enrolled from occupational medicine clinics, were treated with eye drops containing 0.001% GPI in 0.2% HA vehicle three times a day. Ocular surface disease index (OSDI), tear break-up time (T-BUT), Schirmer test, Oxford score, hyperemia and ocular surface symptoms were recorded at patient enrolment (T0), after 1 week (T1) and after 1 month (T2) of treatment. RESULTS: A total of 113 consecutive patients (226 eyes) were included. OSDI score displayed a significant improvement after one week (T0: 39.9 ± 19, T1: 20.8 ± 17.9, T2: 18.4 ± 15.6, p < 0.0001); T-BUT (T0: 5.2 ± 2, T1: 7.7 ± 2.2, T2: 9.7 ± 1.8, p < 0.0001) and Schirmer Test (T0: 6.6 ± 2.4, T1: 9.7 ± 2.7, T2: 12.6 ± 2.6, p < 0.0001) progressively improved from T0 to T2. CONCLUSIONS: trice-daily topic instillation of 0.001% GPI in 0.02% HA vehicle resulted an effective and well tolerated treatment in US patients.

Sex Hormones Related Ocular Dryness in Breast Cancer Women.

BACKGROUND: Dry eye syndrome (DES) is strictly connected to systemic and topical sex hormones. Breast cancer treatment, the subsequent hormonal therapy, the subsequent hyperandrogenism and the early sudden menopause, may be responsible for ocular surface system failure and its clinical manifestation as dry eye disease. This local dryness is part of the breast cancer iatrogenic dryness, which affects overall mucosal tissue in the fragile population of those with breast cancer. METHODS: A literature review regarding the role of sex hormone changes and systemic hormonal replacement treatments (SHRT) in DES available on PubMed and Web of Science was made without any restriction of language. RESULTS: Androgens exert their role on the ocular surface supporting meibomian gland function and exerting a pro-sebaceous effect. Estrogen seems to show a pro/inflammatory role on the ocular surface, while SHRT effects on dry eye are still not well defined, determining apparently contradictory consequences on the ocular surface homeostasis. The role of sex hormones on dry eye pathogenesis is most likely the result of a strict crosstalk between the protective androgens effects and the androgen-modulating effects of estrogens on the meibomian glands. CONCLUSIONS: Patients with a pathological or iatrogenic hormonal imbalance, such as in the case of breast cancer, should be assessed for dry eye disease, as well as systemic dryness, in order to restore their social and personal quality of life.

Challenges in Acanthamoeba Keratitis: A Review.

To review challenges in the diagnosis and management of Acanthamoeba keratitis (AK), along with prognostic factors, in order to help ophthalmologists avoid misdiagnosis, protracted treatment periods, and long-term negative sequelae, with an overarching goal of improving patient outcomes and quality of life, we examined AK studies published between January 1998 and December 2019. All manuscripts describing clinical manifestations, diagnosis, treatment, prognosis, and challenges in short- and long-term management were included. The diagnosis of AK is often challenging. An increased time between symptom onset and the initiation of appropriate therapy is associated with poorer visual outcomes. The timely initiation of standardized antiamoebic therapies improves visual outcomes, decreases the duration of treatment, and reduces the chances of needing surgical intervention. In clinical practice, AK diagnosis is often missed or delayed, leading to poorer final visual outcomes and a negative impact on patient morbidity and quality of life.

Outcomes of routine use of percutaneous access with large-bore introducer sheaths (>21F outer diameter) during endovascular aneurysm repair.

OBJECTIVE: The objective of this study was to evaluate the performance of percutaneous femoral access with large-bore sheaths (>21F outer diameter) mainly employed for thoracic and thoracoabdominal aortic endovascular treatment and to stratify the outcomes on the basis of the introducer size. METHODS: Between December 2015 and December 2018, all consecutive patients who received endovascular repair through a percutaneous approach with a suture-mediated vascular closure device (VCD) and the preclose technique were included in a retrospective single-center study called Totally Percutaneous Approach to Endovascular Treatment of Aortic Aneurysms (PEVAR-PRO). The morphologic characteristics of the access vessels and patients' demographics were recorded, and 30-day closure success was defined as the primary end point. Analysis of the closure success comparing large-bore sheaths vs small-bore sheaths (≤21F outer diameter) was performed after 1:1 propensity score matching of preoperative confounding variables. RESULTS: The closure success rate of the entire study cohort was 94% (622 femoral accesses in 360 patients; median age, 74 years; 84% male). Univariate analysis identified eight different factors associated with failure, but only two remained significant on multivariate analysis: diabetes (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.3-6.2; P = .011) and common femoral artery stenosis >50% (OR, 4.5; 95% CI, 1.3-13.7; P = .019). After propensity score matching (1:1, 172 femoral accesses per group), closure success rate was not significantly different between large-bore and small-bore sheaths (90.7% vs 93.0%; P = .43). Multivariate analysis of the large-sheath group identified two factors associated with failure: small (<9 mm) femoral arteries (OR, 6.9; 95% CI, 1.5-31.6; P = .13) and access vessel calcifications involving more than one-third of the circumference (OR, 7.9; 95% CI, 2.1-29.4; P = .002). Neither previous femoral cutdown (44 accesses [23%]) nor percutaneous closure with VCDs (38 accesses [20%]) affected the closure success rate in the large-sheath group. Closure failure did not significantly increase the need for postoperative blood transfusions or hospital length of stay. CONCLUSIONS: Off-label use of VCDs and the preclose technique for percutaneous approach with large-bore sheaths needed for complex aortic endovascular procedures is safe and feasible. Closure success rate is not significantly different from that obtained with on-label application of VCDs with smaller sheaths.

Does Endogenous Endophthalmitis Need a More Aggressive Treatment?

Topic: To focus on endogenous endophthalmitis management, particularly etiology-based medical and surgical therapy.Methods: Literature search of published studies from July 1990 to February 2019 on endogenous endophthalmitis available on PubMed was made without any language constraints.Results: A total of 78 articles were retrieved from 728 initially analyzed and 62 studies were included. Although the superiority of vitrectomy over tap and inject techniques is controversial, the most recent publications favor an early surgical approach for endogenous endophthalmitis. Vitrectomy is useful in severe cases complicated by marked vitreous opacity, retinal detachment, poor initial visual acuity, and more virulent pathogens. Oral or intravenous antibiotics are also necessary to treat systemic infection. Vitrectomy is superior to blood cultures in diagnosing the etiology of infection.Conclusions: Endogenous endophthalmitis is an important cause of visual acuity impairment. Prompt treatment with appropriate use of pharmacological or surgical therapy is mandatory to preserve visual function.Abbreviations: IOP: intra-ocular pressure; AIDS: acquired immune deficiency syndrome; EVS: endophthalmitis vitrectomy study; CEVE: complete and early vitrectomy for endophthalmitis.

Volumetric analysis of aneurysm thrombosis after thoracic endovascular aortic repair predicts postoperative changes in platelet count and coagulation parameters.

BACKGROUND: The aim of this study was to investigate the predictors of blood count changes and coagulation parameters alterations after thoracic aortic endovascular repair (TEVAR). METHODS: Fifty patients (41 males, age 72±7 years) submitted between 2007 and 2009 to elective TEVAR for non-dissecting aortic lesions, without major associated surgical procedures, were analyzed. Blood count and coagulation parameters were recorded pre-operatively and daily up to postoperative day 5. The volume of new thrombus formed after TEVAR (TV) was calculated comparing pre- and post-operative computed tomography scans with a semi-automatic method by two independent examiners. Pre- intra-, and postoperative variables, including TV, were tested for a possible effect on changes in laboratory values and transfusion requirements using a stepwise multiple regression model analysis. RESULTS: In the multivariable model, TV and associated surgical procedures were significantly associated with maximum platelets decrease (P=0.021, and P=0.029, respectively), while only TV remained a significant predictor for maximum prothrombin time increase (P=0.003). Maximum aneurysm diameter (P=0.041), procedural time (P=0.027), and TV (P=0.047) were also significant predictors of transfusion requirement. CONCLUSIONS: TEVAR is associated with consumption of platelets and coagulative factors, which seems to be associated with the amount of perioperative aneurysm thrombosis. The latter may also help to predict perioperative transfusion requirement.

Multicenter randomized trial comparing compression with elastic stocking versus bandage after surgery for varicose veins.

OBJECTIVES: Postoperative limb compression is widely used after venous surgery to prevent thromboembolism and to reduce hemorrhage, edema, hematoma, and pain. Only limited studies have been published regarding the most adequate postoperative compression therapy after varicose vein surgery. This study evaluated the effectiveness of a new stocking kit used for postoperative limb compression. METHODS: The study compared the clinical practicability, ease to use, effectiveness, and safety of a postoperative stocking system (23 to 32 mmHg at the ankle) with compression bandages (control group). This prospective, randomized, open-label clinical trial, was performed in three Italian centers specializing in venous surgery. Sixty consecutive patients (classification CEAP C2,(S)) underwent unilateral varicose vein surgery at one of the three centers. After surgery, patients were randomized for postoperative compression therapy with a new stocking system (Sigvaris Postoperative Kit; Ganzoni Sigvaris Corp, Winterthur, Switzerland) or standard stretch bandages (30 patients per group). Primary end points were incidence of venous thromboembolism, hemorrhage, limb hematoma, or edema. RESULTS: No episodes of venous thromboembolism were observed. The mean area of thigh hematoma on postoperative days 7 and 14 was 75.70 cm² and 2.93 cm², respectively, for the stocking group, and 92.97 cm² and 5.42 cm² for the bandage group (not significant). On postoperative day 7, edema was found in 50% of the patients wearing bandages and in 20% of the patients wearing the stocking kit, which was a significant reduction. No statistical difference was recorded for postoperative pain; however, better patient acceptance and quality of life after the operation were recorded in the stocking group. CONCLUSION: Patients can be effectively treated with the Sigvaris Postoperative Kit. Patients treated with stockings have less edema compared with standard bandaging, and the application of the stocking kit improves patient quality of life and compliance with postoperative compression therapy.

Glomerular filtration rate after left renal vein division and reconstruction during infrarenal aortic aneurysm repair.

OBJECTIVES: The study assessed the effect on postoperative renal function of left renal vein (LRV) division and reconstruction by direct reanastomosis or graft interposition during infrarenal abdominal aortic aneurysm (AAA) repair. METHODS: Between January 2001 and March 2006, 1189 patients underwent elective open repair of infrarenal AAAs. LRV division was performed in 15 (1.3%) and its reconstruction in all but one (LRV group), where the LRV was occluded. Patients' glomerular filtration rates (GFRs) were retrospectively estimated through postoperative day 4 by using the Cockcroft-Gault equation and compared with the GFRs of 56 controls undergoing AAA repair without LRV division (control group) randomly identified from a prospectively compiled database in a 4:1 ratio. Post hoc 1:1 case-matched analysis was also performed. Statistical analyses were performed as appropriate. RESULTS: Comparison of demographics and risk factors revealed no statistically significant differences between the two groups with the exception of the following: AAAs were larger in LRV group (71.4 +/- 17.1 mm vs 56.0 +/- 14.6 mm; P = .003) and preoperative GFR was lower in LRV group (65.3 +/- 19.0 mL/min/1.73 m(2) vs 82.8 +/- 22.3 mL/min/1.73 m(2); P = .009). Postoperatively, the trend of GFR with time did not differ between groups (P = .33). The variation of GFR at day 4 after surgery compared with preoperative values was not different either (5.6 +/- 12.6 mL/min/1.73 m(2) vs 1.0 +/- 15.5 mL/min/1.73 m(2); P = .67). A further 1:1 case-matched multivariate analysis of variance, matching patients and controls by AAA size and preoperative GFR, showed no difference in trend of GFR with time between groups (P = .15). Operative time was not significantly longer in LRV group (148.4 +/- 35.8 minutes vs 131.0 +/- 40.3 minutes; P = .07). No differences between groups were found for blood loss (585.7 +/- 264.2 mL vs 567.7 +/- 222.5 mL; P = .88), perioperative complications (5 vs 8; P = .12), or hospital length of stay (6.2 +/- 1.8 days vs 5.5 +/- 1.2 days; P = .10). A 6-month follow-up of renal function available in 12 patients of LRV group showed no significant decrease in GFR compared with postoperative values (70.8 +/- 24.8 mL/min/1.73 m(2) vs 69.1 +/- 23.5 mL/min/1.73 m(2); P = .86). At duplex scan, the reconstructed LRV could be insonated in nine of these 12 patients and all were patent. CONCLUSIONS: LRV division during AAA repair was associated with larger aneurysms and preoperative subclinical renal function impairment. In these patients, LRV reconstruction was associated with the maintenance of preoperative renal functional status without significantly lengthening of operative time or increasing the complications from surgery.