Lacrimal Flow Research Articles

In silico evaluation of corneal patch eluting anti-VEGF agents concept

This study introduces a novel approach utilizing a temporary drug-eluting hydrogel corneal patch to prevent neovascularization, alongside a numerical predictive tool for assessing the release and transport kinetics of bevacizumab (BVZ) after the keratoplasty. A key focus was investigating the impact of tear film clearance on the release kinetics and drug transport from the designed corneal patch. The proposed tear drug clearance model incorporates the physiological mechanism of lacrimal flow (tear turnover), distinguishing itself from previous models. Validation against experimental data confirms the model’s robustness, despite limitations such as a 2D axisymmetrical framework and omission of blink frequency and saccadic eye movements potential effects. Analysis highlights the significant influence of lacrimal flow on ocular drug transport, with the corneal patch extending BVZ residence time compared to topical administration. This research sets the stage for exploring multi-layer drug-eluting corneal patches as a promising therapeutic strategy in ocular health.

Applying Different Conditions in the OphthalMimic Device Using Polymeric and Hydrogel-Based Hybrid Membranes to Evaluate Gels and Nanostructured Ophthalmic Formulations.

The OphthalMimic is a 3D-printed device that simulates human ocular conditions with artificial lacrimal flow, cul-de-sac area, moving eyelid, and a surface to interact with ophthalmic formulations. All tests with such a device have used a continuous artificial tear flow rate of 1 mL/min for 5 min. Here, we implemented protocol variations regarding the application time and simulated tear flow to increase the test's discrimination and achieve reliable performance results. The new protocols incorporated the previously evaluated 0.2% fluconazole formulations containing or not chitosan as a mucoadhesive component (PLX16CS10 and PLX16, respectively) and novel moxifloxacin 5% formulations, either in a conventional formulation and a microemulsion (CONTROL and NEMOX, respectively). The flow rate was reduced by 50%, and a pre-flow application period was also included to allow formulation interaction with the membrane. The OphthalMimic model was used with both polymeric and hydrogel-based hybrid membranes, including a simulated eyelid. Lowering the flow made it feasible to prolong the testing duration, enhancing device discrimination potential. The hydrogel membrane was adequate for testing nanostructure formulations. The OphthalMimic device demonstrated once again to be a versatile method for evaluating the performance of ophthalmic drug formulations with the potential of reducing the use of animals for experimentation.

Hydrogel-based hybrid membrane enhances in vitro ophthalmic drug evaluation in the OphthalMimic device

Envisaging to improve the evaluation of ophthalmic drug products while minimizing the need for animal testing, our group developed the OphthalMimic device, a 3D-printed device that incorporates an artificial lacrimal flow, a cul-de-sac area, a moving eyelid, and a surface that interacts effectively with ophthalmic formulations, thereby providing a close representation of human ocular conditions. An important application of such a device would be its use as a platform for dissolution/release tests that closely mimic in vivo conditions. However, the surface that artificially simulates the cornea should have a higher resistance (10 min) than the previously described polymeric films (5 min). For this key assay upgrade, we describe the process of obtaining and thoroughly characterizing a hydrogel-based hybrid membrane to be used as a platform base to simulate the cornea artificially. Also, the OphthalMimic device suffered design improvements to fit the new membrane and incorporate the moving eyelid. The results confirmed the successful synthesis of the hydrogel components. The membrane’s water content (86.25 ± 0.35 %) closely mirrored the human cornea (72 to 85 %). Furthermore, morphological analysis supported the membrane’s comparability to the natural cornea. Finally, the performance of different formulations was analysed, demonstrating that the device could differentiate their drainage profile through the viscosity of PLX 14 (79 ± 5 %), PLX 16 (72 ± 4 %), and PLX 20 (57 ± 14 %), and mucoadhesion of PLXCS0.5 (69 ± 1 %), PLX16CS1.0 (65 ± 3 %), PLX16CS1.25 (67 ± 3 %), and the solution (97 ± 8 %). In conclusion, using the hydrogel-based hybrid membrane in the OphthalMimic device represents a significant advancement in the field of ophthalmic drug evaluation, providing a valuable platform for dissolution/release tests. Such a platform aligns with the ethical mandate to reduce animal testing and promises to accelerate the development of safer and more effective ophthalmic drugs.

OphthalMimic: A new alternative apparatus without animal tissue for the evaluation of topical ophthalmic drug products

The necessity of animal-free performance tests for novel ophthalmic formulation screening is challenging. For this, we developed and validated a new device to simulate the dynamics and physical–chemical barriers of the eye for in vitro performance tests of topic ophthalmic formulations. The OphthalMimic is a 3D-printed device with an artificial lacrimal flow, a cul-de-sac area, a support base, and a simulated cornea comprised of a polymeric membrane containing poly-vinyl alcohol 10 % (w/v), gelatin 2.5 % (w/v), and different proportions of mucin and poloxamer, i.e., 1:1 (M1), 1:2 (M2), and 2:1 (M3) w/v, respectively. The support base is designed to move between 0° and 50° to replicate the movement of an eyelid. We challenged the model by testing the residence performance of poloxamer®407 16 % and poloxamer®407 16 % + chitosan 1 % (PLX16CS10) gels containing fluconazole. The test was conducted with a simulated tear flow of 1.0 mL.min−1 for 5 min. The OphthalMimic successfully distinguished PLX16 and PLX16C10 formulations based on their fluconazole drainage (M1: 65 ± 14 % and 27 ± 10 %; M2: 58 ± 6 % and 38 ± 9 %; M3: 56 ± 5 % and 38 ± 18 %). In conclusion, the OphthalMimic is a promising tool for comparing the animal-free performance of ophthalmic formulations.

Dynamic Ex Vivo Porcine Eye Model to Measure Ophthalmic Drug Penetration under Simulated Lacrimal Flow.

Animal models are still used in the research and development of ophthalmic drug products, mainly due to the difficulty in simulating natural physiological conditions with in vitro models, as there is a lack of dynamic protection mechanisms. Therefore, developing alternative ophthalmic models that evaluate drug penetration in the cornea while applying dynamic protection barriers is a contemporary challenge. This study aimed to develop a dynamic ex vivo model using porcine eyes with a simulated lacrimal flow to evaluate the performance of pharmaceutical drug products. A glass donor cell to support a simulated tear flow was designed, optimized, and custom-made. The system was challenged with different formulations (with fluconazole) including excipients with different viscosities (poloxamer 407) and mucoadhesive properties (chitosan). The results were compared to those obtained from a conventional excised cornea model mounted in Franz-type diffusion cells. The dynamic model could differentiate formulations, while the static model did not, overestimating ex vivo drug penetrated amounts. Hence, the dynamic model with simulated tear flow showed to be a simple and promising new alternative method for the drug penetration of ophthalmic formulations that ultimately can reduce the number of animals used in research.

The importance of clinical presentation on long-term outcomes of external dacryocystorhinostomies: Our experience on 245 cases.

External dacryocystorhinostomy (EXT-DCR) is a surgical approach commonly used to treat post-canalicular acquired lacrimal obstruction whose success rate has been described, equally with endoscopic DCR, to be superior to other available treatments. At San Raffaele Hospital, Milan (Italy), from January 2008 to December 2020, 245 EXT-DCRs were performed. All patients underwent routine pre-operative work-up including Jones tests and probing and irrigation of the lacrimal pathway; when necessary, a multidisciplinary approach with nasal endoscopy was performed. The surgical approach was followed by positioning of a bicanalicular stent which was left in place for 6 months. Success was defined as resolution of clinical signs/symptoms and free lacrimal flow on functional test. Of the cases enrolled, 26.9% were treated for recurrent epiphora (group 1), and 73.1% for epiphora associated with chronic dacryocystitis (group 2). After a median follow-up of 71 months, group 1 had success at T0 (1 month) and T1 (long-term) of 81.8% and 60.6%, respectively, compared to 93.8% and 77.7% in group 2. Statistical analysis showed a significant association with surgery both at T0 (p = 0.018) and T1 (p = 0.012) with group 2 showing better outcomes. Additionally, the cosmetic outcome of the external scar was defined as invisible in 91.8% of cases and slightly visible in 8.2%. External dacryocystorhinostomy provides long-term reliable results particularly in case of chronic dacryocystitis. Moreover, the optimal esthetic outcome of the external scar should be no longer considered the only guiding principle of treatment modality, particularly in the elderly.

Endoscopic endonasal dacryocystorhinostomy-an experience in a tertiary care hospital

<p><strong>Background:</strong> Dacryocystorhinostomy is a surgical procedure by which the lacrimal flow is diverted into the nasal cavity by making an opening in the lacrimal sac when the nasolacrimal duct gets blocked. The operation can be carried out using either an external or endonasal surgical approach.</p><p><strong>Methods:</strong> This is a clinical observational study done on 50 patients with chronic dacryocystitis with obstruction at the level of sac or nasolacrimal duct. This study was conducted at Dr. Shankarrao Chavan government medical college, Nanded, during the period of 2 years (2018-2020). Patients were evaluated and operated for endoscopic endonasal dacryocystorhinostomy.</p><p class="Default"><strong>Results:</strong> The mean age of studied cases was 33.92±12.13 years. The M:F ratio was 0.78. Epiphora was the predominant complaint in all cases 100%. Swelling of lacrimal sac was present in 24% cases and Pain on affected side was present in 18% cases. 6% patients had fistula on the side of block. 12% patients had mucocele and 14% patients had pyocele on the affected side. Left and right side was involved in 54% and 40% cases respectively. The disease presented bilaterally in 06% cases. 80% patients had no complications after endonasal endoscopic dacryocystorhinostomy (EEDCR) surgery. Rate of surgical success was 92%.</p><p class="Default"><strong>Conclusions:</strong> Nasolacrimal duct obstruction is more common among females and in middle aged persons. EEDCR is treatment which provides patients relief from the symptoms without any scar and also preserves nasolacrimal pump system with high success rate. It may prove better surgical technique in chronic dacryocystitis.</p>

Long-term results of a balloon-assisted endoscopic approach in failed dacryocystorhinostomies.

PurposeEndoscopic endonasal balloon-assisted dacryoplasty is a minimally invasive surgical approach that can be applied after failure of dacryocystorhinostomy with recurrence of distal acquired lacrimal obstruction.MethodsAt the Department of Otolaryngology, San Raffaele Hospital, Milan (Italy), from December 2016 to October 2020, 14 patients underwent trans-nasal balloon-assisted dacryoplasty after a failed dacryocystorhinostomy (both external and endoscopic endonasal). The routinary pre-operative work-up included multidisciplinary study of the lacrimal disease, which consisted in primary ophthalmological and otorhinolaryngological visits associated with nasal endoscopy, in which a radiological exam was added if needed. The surgical approach includes pneumatic enlargement of the stenotic rhinostomy, created during the primary dacryocystorhinostomy, using a high-pressure trans-nasal balloon catheter. Anatomical success was considered when the ostium was patent upon irrigation, while functional success was considered as resolution of epiphora or free lacrimal flow on functional test.ResultsAmong 14 patients included and after a mean follow-up of 19.5 months (range 13–51 months), anatomic success was achieved in 100% of patients and functional success was achieved in the 85.7% (12/14). Operative time ranged from 9 to 28 min (mean 18 min) and no complications were reported.ConclusionTrans-nasal balloon-assisted dacryoplasty is a mini-invasive surgical approach to treat failed dacryocystorhinostomies with reliable and stable outcomes in the long term. The absence of post-surgical complications, high success rate and short operative time are the main features of this innovative procedure.

Go Ask Your Patients! PSS-QoL Reported Perception of Dryness Correlates With Lacrimal and Salivary Flow in Primary Sjögren's Syndrome.

Introduction/Objectives: The patient perspective is an essential outcome parameter in the quest for effective therapy in primary Sjögren's Syndrome (PSS). The EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is recommended by EULAR to quantify patient's symptom burden and has been used in several clinical trials. Surprisingly, the patient's perception of dryness quantified with ESSPRI does not correlate with objective measures of salivary or lacrimal flow. Thus, we evaluated a newly developed assessment tool-the Primary Sjögren's Syndrome Quality of Life Questionnaire (PSS-QoL)—for quantifying symptoms of dryness in comparison with the ESSPRI and objective measurements of salivary and lacrimal flow.Methods: Data of patients from the PSS registry of the Medical University of Graz fulfilling the 2016 ACR/EULAR classification criteria for PSS were analyzed. The patient perspective was analyzed by PSS-QoL, ESSPRI, Xerostomia Inventory (XI) and Ocular Surface Disease Index (OSDI). Sicca signs were measured with Schirmer's test, unstimulated salivary flow test (USF) and stimulated salivary flow test (SSF). ESSDAI (EULAR Sjögren's Syndrome Disease Activity Index) and EGA (Evaluator Global Assessment, numeric rating scale from 0 to 10) were obtained. In addition, free light chains (FLC) κ and λ, rheumatoid factor (RF) IgM and IgA were determined.Results: Data from 123 PSS patients were analyzed; 91.9% (n = 113) were female, with a mean disease duration of 6.2 (±5.3) years and mean age of 60.1 (±12.4) years. PSS-QoL-dryness revealed significant negative correlations with Schirmer's test (r = −0.31, p < 0.05) and SSF-test (r = −0.390, p < 0.01). In contrast, we found no significant correlation between ESSPRI-dryness and any objective dryness test. Lower perceived dryness was associated with higher immunological activity determined by increased levels of IgG, FLC and RF-IgA. Whereas patients with only subjective signs of dryness had lower immunological activity.Discussion: Patients' perception of dryness assessed by PSS-QoL correlates with objective measurements of salivary gland function while ESSPRI-dryness did not. Based on the PSS-QoL and objective measures of dryness two distinct groups of PSS patients could be distinguished, which may have implications in daily practice and future clinical studies.

The use of Schirmer strips to measure salivary and lacrimal flow in non-Sj\xf6gren patients

IntroductionOral and ocular dryness are the most common symptoms reported during ophthalmological and dental examinations. It is becoming a serious and growing problem due to the huge variety of affecting factors and with population aging.ObjectivesThe purpose was to demonstrate an application of the Schirmer test for xerostomia. Subsequently, to compare and correlate the results achieved from the lacrimal Schirmer test and salivary Schirmer test in non-Sjögren patients.MethodsStudy group consisted of 642 patients with/without subjective or/and objective symptoms of dry eye or mouth who did not fulfill the criteria for diagnosis of Sjögren syndrome. The lacrimal Schirmer test (lST) and the salivary Schirmer tests (sST) were performed (sSTm was put on the floor of the mouth, sSTp in front of the parotid gland duct). The results were recorded after 1 min (sSTm), 3 min (sSTp), and 5 min (lST).ResultsThe lST and sST test scores were considerably higher in the healthy group than in others, p < 0.001. The results of sST1 and sST2 decreased with the appearance of subjective and objective symptoms, p < 0.001. There were positive correlations between lST and sSTm outcomes between the groups, p < 0.001.ConclusionsWe present the Schirmer test adapted to measure salivary gland hypofunction that is a time-saving tool in our daily practice. Results of this study reveal an excellent correlation between the eye Schirmer test and the salivary Schirmer tests.Clinical relevanceThe salivary Schirmer tests seem to be rapid, convenient, and reliable objective screening tools for salivary gland hypofunction in non-Sjögren patients.

Besifloxacin liposomes with positively charged additives for an improved topical ocular delivery

Topical ophthalmic antibiotics show low efficacy due to the well-known physiological defense mechanisms of the eye, which prevents the penetration of exogenous substances. Here, we aimed to incorporate besifloxacin into liposomes containing amines as positively charged additives and to evaluate the influence of this charge on drug delivery in two situations: (i) iontophoretic and (ii) passive treatments. Hypothesis are (i) charge might enhance the electromigration component upon current application improving penetration efficiency for a burst drug delivery, and (ii) positive charge might prolong formulation residence time, hence drug penetration. Liposomes elaborated with phosphatidylcholine (LP PC) or phosphatidylcholine and spermine (LP PC: SPM) were stable under storage at 6 ºC for 30 days, showed mucoadhesive characteristics, and were non-irritant, according to HET-CAM tests. Electron paramagnetic resonance spectroscopy measurements showed that neither the drug nor spermine incorporations produced evident alterations in the fluidity of the liposome's membranes, which retained their structural stability even under iontophoretic conditions. Mean diameter and zeta potential were 177.2 ± 2.7 nm and − 5.7 ± 0.3 mV, respectively, for LP PC; and 175.4 ± 1.9 nm and + 19.5 ± 1.0 mV, respectively, for LP PC:SPM. The minimal inhibitory concentration (MIC) and the minimal bactericide concentration (MBC) of the liposomes for P. aeruginosa showed values lower than the commercial formulation (Besivance). Nevertheless, both formulations presented a similar increase in permeability upon the electric current application. Hence, liposome charge incorporation did not prove to be additionally advantageous for iontophoretic therapy. Passive drug penetration was evaluated through a novel in vitro ocular model that simulates the lacrimal flow and challenges the formulation resistance in the passive delivery situation. As expected, LP PC: SPM showed higher permeation than the control (Besivance). In conclusion, besifloxacin incorporation into positively charged liposomes improved passive topical delivery and can be a good strategy to improve topical ophthalmic treatments.

English

BACKGROUND Dacryocystorhinostomy (DCR) operation is the gold standard treatment for management of chronic dacryocystitis due to nasolacrimal duct block. This operation directs the lacrimal flow into the nasal cavity creating an artificial opening made at the level of lacrimal bone, thus obtaining a low-pressure lacrimal bypass system which will relieve epiphora and dacryocystitis. But the commonest reason for failure of this surgery is closure of the rhinostomy (neo-ostium). To overcome this difficulty, silicone tube catheter stent insertion has been advocated. Here in this study, we wanted to compare the success rate of endoscopic DCR with or without silicone tube catheter (STC) stent. METHODS This study was a prospective study conducted among 50 patients divided in to two equal groups randomly. One group underwent Endoscopic DCR with silicone tube catheter stent and another group underwent DCR without stent. We compared outcomes of both groups subjectively with five-point scale and objectively examined patency of the stoma by syringing with water postoperatively after 3 months and results were compared. RESULTS During subjective evaluation, we used five-point scales to get the grade of epiphora relief. First three grades (grade 1 to grade 3) were considered as success. We got an overall success rate of 92 % in without stent group and we got 88 % success rate in silicone tube catheter stent group. CONCLUSIONS Surgical success for Endoscopic DCR surgery encompassed both anatomical patency and symptom relief. We found overall success rate of 92 % in without stent group and 88 % success rate in silicone tube catheter stent group which were closely comparable to other studies. We also found failure due to granulation tissue formation in STC stent group. So the role of stent is yet to be confirmed and further large scale trials are needed. KEYWORDS Endoscopic DCR, Silicone Tube Catheter (STC) Stent

Role of nasolacrimal duct probing in pre-operative endo-dacryocystorhinostomy

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Infection s and facial trauma are likely to disrupt the lacrimal flow in the region of the medial canthus. Individuals with epiphora refractory to topical medication and secondary to an obstructive aetiology were subjected to nasolacrimal duct probing prior to endo-nasal-dacrocystorhinostomy, to identify the likely site of obstruction, cannalicular, common cannalicus or in the nasolacrimal duct.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; 40 adult subjects of long duration epiphora were selected from the outpatient clinics of otorhinolaryngology and opthalmology services of Dayanand Medical College and Hospital, Ludhiana. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; On pre-operative lacrimal probing, the block was detected at a distance of greater than 3 cm in 26 sides (65%) and less than 3 cm in 14 sides (35%).&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; In patients of epiphora, the naso-lacrimal system had an obstruction, in the duct and usually at a distance of greater than 3 cm from the punctum.&lt;/p&gt;

Endoscopic endonasal balloon-dacryoplasty in failed dacryocystorhinostomy.

Endoscopic endonasal balloon-assisted dacryoplasty is a minimally-invasive surgical procedure that can be used in recurrent epiphora, a common pathology in both adulthood and childhood. We present a retrospective case series of eight patients who underwent trans-nasal balloon-assisted dacryoplasty after a failed external or endoscopic dacryocystorhinostomy, from March 2019 to January 2020, at the Department of Otolaryngology, San Raffaele Hospital, Milan, Italy. All patients underwent routine preoperative work-up including fluorescein test (Jones test I-II), probing and irrigation of the lacrimal pathway and nasal endoscopy. Because of the recurrent nature of the pathology, pre-operatory computed tomography scan or dacryocystography was not performed. The surgical procedure was based on enlargement of the stenotic neorhinostomy created by primary dacryocystorhinostomy through the use of a high-pressure balloon catheter. Anatomical success was defined as a patent ostium on irrigation, whereas functional success was defined as free lacrimal flow on functional test and resolution of epiphora. Anatomic and functional success was achieved in 100% of patients. Operative time ranged from 9 to 22 min (mean 16 min). No significant complications were reported. Our results indicate that trans-nasal balloon-assisted dacryoplasty can be considered as a safe and reliable surgical approach after a failed primary dacryocystorhinostomy. The shorter surgical time and reduced post-operative complication rates are the main advantages of this procedure.

Five- and 10-Year Outcomes for Primary Endoscopic Dacryocystorhinostomy: Failure Rate and Risk Factors.

Endoscopic dacryocystorhinostomy (eDCR) is the preferred approach for nasolacrimal duct obstruction, yet quality data on long-term outcomes is lacking. A retrospective study in a single, academic institution. To assess the 5- and 10-year success rates of eDCR, and its associated risks. All eDCRs conducted at Kaplan Medical Center between the years 2002-2017 were included. For long-term follow-up analysis, two subgroups with a minimum of documented 5- and 10-year follow-up after surgery were defined. Surgical success was defined by both anatomical (observed patent lacrimal flow) and functional (symptomatic relief) success. Data was collected from the hospital's electronic medical records and was completed by phone interviews. Pre-, intra-, and postoperative variables were collected and stratified by multivariate analysis. After exclusions, 321, 168, and 65 patients were included for immediate, 5- and 10-year outcome analysis, respectively. Overall success rates were 92.5%, 86.3%, and 80%, respectively. The anatomical success rates were 93.8%, 89.9%, and 86.1%, respectively. Multivariate analysis revealed that older age (P < .001, P = .001) previous smoking (P = .043, P = .037), and postoperative complains of epiphora (even when a successful irrigation was observed, P < .001, P = .01) were all associated with eDCR failure 5 and 10 years following surgery. Male gender was also associated with eDCR failure (5 years, P = .045; 10 years, P = .063). Despite decreased rates over time, eDCR is beneficial for the majority of patients also at 10 years following surgery. Older age, smoking, postoperative epiphora, and male gender are related to long-term failure and should be discussed with the patients before surgery. 3b Laryngoscope, 131:10-16, 2021.

Dacryocystorhinostomy: Evolution of endoscopic techniques after 498 cases.

Endoscopic dacryocystorhinostomy is a well-known surgical practice used to treat nasolacrimal duct obstruction and widely considered as a valid alternative to external approaches. We present a retrospective case series of 498 endoscopic dacryocystorhinostomies on 401 patients, from July 2004 to May 2018, at the Department of Otolaryngology, San Raffaele Hospital, Milan, Italy. Of the 498 procedures, 426 were unilateral and 72 were bilateral dacryocystorhinostomy. All patients underwent routine preoperative workup including fluorescein test (Jones test 1-2), probing and irrigation of the lacrimal way, nasal endoscopy, and maxilla-facial computed tomography scan. Surgical technique was based on nasal endoscopic dacryocystorhinostomy followed by positioning of a Catalano's silicone stent, which was left in place for about 3 months. Anatomical success was defined as a patent ostium on irrigation, whereas functional success was defined as free lacrimal flow on functional test and resolution of epiphora. Anatomic success was achieved in 91.54% cases in primary dacryocystorhinostomy and in 89.36% after revision, whereas functional success was obtained in 90.4% in primary and 85.1% in secondary dacryocystorhinostomies. After a second revision of endoscopic dacryocystorhinostomy, anatomical success was achieved in 90.1% and functional success in 88.7% of procedures. Our results confirm that endoscopic dacryocystorhinostomy can be considered as a valid surgical approach to primary nasolacrimal duct obstruction and revision cases. The key aspects in achieving functional and anatomical results are meticulous surgical procedure and precise follow-up.

Proteins Regulating Salivary and Lacrimal Flow in Xerostomia and Dry Eye Syndrome

Proteins Regulating Salivary and Lacrimal Flow in Xerostomia and Dry Eye Syndrome

Longitudinal Changes in the European League Against Rheumatism Sjögren's Syndrome Patient Reported Index in Real-Life Practice

Objective. To investigate longitudinal changes in the European League Against Rheumatism (EULAR) Sjogren’s syndrome patient reported index (ESSPRI) and to study the clinical features associated with favorable ESSPRI changes in primary Sjogren’s syndrome (pSS). Methods. At baseline and after a median period of 6.6 years, 41 pSS patients were evaluated using the ESSPRI, EULAR Sjogren’s syndrome disease activity index (ESSDAI), short-form 36, xerostomia inventory (XI), and visual analog scale (VAS) scores for symptoms. The favorable subgroup included patients who were stable or showed improved to satisfactory symptom status (ESSPRI＜5) and the unfavorable subgroup included those with stable or worsening to an unsatisfactory symptom status (ESSPRI ≥5). Results. Median ESSPRI increased from 4.11 to 5.33 (p＜0.05), although XI scores (p=0.01) and oral dryness (p＜0.05) were significantly decreased. Serum immunoglobulin G level was significantly reduced (p＜0.001) but ESSDAI scores were unchanged. Six (14.6%) patients showed clinical improvement in ESSDAI, and 11 (26.8%) showed improvement in ESSPRI. On comparing the favorable (n=17) and unfavorable (n=24) subgroups, the former exhibited significantly lower VAS scores for sicca and depression and XI and ESSPRI scores at baseline (all p＜0.05) and more lacrimal flow (p＜0.05). The favorable subgroup received a significantly lower cumulative dose of pilocarpine and glucocorticoids (both p＜0.05). Conclusion. About 25% of pSS patients showed clinically significant ESSPRI improvement and about 40% showed a favorable ESSPRI course. Because the favorable subgroup had more lacrimal flow and less sicca symptoms at baseline, long-term patient-derived outcomes could depend on residual exocrine function at pSS diagnosis. (J Rheum Dis 2019;26:191-199)

Pilocarpine and artificial saliva for the treatment of xerostomia and xerophthalmia in Sjögren syndrome: a double-blind randomized controlled trial.

Sjögren syndrome (SS) is associated with xerostomia and xerophthalmia. Pilocarpine has been shown to stimulate the secretion of saliva. To investigate and compare the efficacy of pilocarpine and artificial saliva as symptomatic treatments for xerostomia and xerophthalmia in patients with SS. A double-blind randomized controlled study was performed. A total of 72 patients with SS were assigned randomly to receive 10 drops of pilocarpine (5mg) or 10 drops of artificial saliva orally, three times daily for 12weeks. Whole saliva and tear flow were evaluated at baseline and periodically throughout the study to provide a global assessment of dryness and to report any adverse effects. Patients receiving pilocarpine had a statistically significant improvement in their salivary flow (P<0·001), lacrimal flow (P<0·001) and their subjective global assessment (P<0·001), compared with patients who received artificial saliva. The most common side-effects were sialorrhoea and nausea. Pilocarpine is more effective than artificial saliva for enhancing salivary and lacrimal secretion in patients with SS. This is the first study to compare the efficacy of pilocarpine and artificial saliva for the treatment of xerostomia and xerophthalmia in SS.

Randomized Controlled Trial of Rituximab and Cost-Effectiveness Analysis in Treating Fatigue and Oral Dryness in Primary Sjögren's Syndrome.

To investigate whether rituximab, an anti-B cell therapy, improves symptoms of fatigue and oral dryness in patients with primary Sjögren's syndrome (SS). We conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial that included health economic analysis. Anti-Ro-positive patients with primary SS, symptomatic fatigue, and oral dryness were recruited from 25 UK rheumatology clinics from August 2011 to January 2014. Patients were centrally randomized to receive either intravenous (IV) placebo (250 ml saline) or IV rituximab (1,000 mg in 250 ml saline) in 2 courses at weeks 0, 2, 24, and 26, with pre- and postinfusion medication including corticosteroids. The primary end point was the proportion of patients achieving a 30% reduction in either fatigue or oral dryness at 48 weeks, as measured by visual analog scale. Other outcome measures included salivary and lacrimal flow rates, quality of life, scores on the European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient Reported Index and EULAR Sjögren's Syndrome Disease Activity Index, symptoms of ocular and overall dryness, pain, globally assessed disease activity, and cost-effectiveness. All 133 patients who were randomized to receive placebo (n = 66) or rituximab (n = 67) were included in the primary analysis. Among patients with complete data, 21 of 56 placebo-treated patients and 24 of 61 rituximab-treated patients achieved the primary end point. After multiple imputation of missing outcomes, response rates in the placebo and rituximab groups were 36.8% and 39.8%, respectively (adjusted odds ratio 1.13 [95% confidence interval 0.50, 2.55]). There were no significant improvements in any outcome measure except for unstimulated salivary flow. The mean ± SD costs per patient for rituximab and placebo were £10,752 ± 264.75 and £2,672 ± 241.71, respectively. There were slightly more adverse events (AEs) reported in total for rituximab, but there was no difference in serious AEs (10 in each group). The results of this study indicate that rituximab is neither clinically effective nor cost-effective in this patient population.