Ocular Surface Disease as Extraesophageal Gastroesophageal Reflux Disease Manifestation: A Specific Therapeutic Strategy.

PURPOSE: Gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) are common gastrointestinal disorders with extraesophageal manifestations (EGERD). Studies showed a correlation between GERD/LPR and ocular discomfort. Our aim was to report the prevalence of ocular involvement in patients with GERD/LPR, describe clinical and biomolecular manifestations, and provide a treatment strategy for this novel EGERD comorbidity. METHODS: Fifty-three patients with LPR and 25 healthy controls were enrolled in this masked randomized controlled study. Fifteen naive patients with LPR were treated with magnesium alginate eye drops and oral therapy (magnesium alginate and simethicone tablets) with a 1-month follow-up. Clinical ocular surface evaluation, Ocular Surface Disease Index questionnaire, tear sampling, and conjunctival imprints were performed. Tear pepsin levels were quantified by ELISA. Imprints were processed for human leukocyte antigen-DR isotype (HLA-DR) immunodetection and for HLA-DR, IL8, mucin 5AC (MUC5AC), nicotine adenine dinucleotide phosphate (NADPH), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY) transcript expression (PCR). RESULTS: Patients with LPR had significantly increased Ocular Surface Disease Index ( P < 0.05), reduced T-BUT ( P < 0.05), and higher meibomian gland dysfunction ( P < 0.001) compared with controls. After treatment, tear break-up time (T-BUT) and meibomian gland dysfunction scores improved to normal values. Pepsin concentration increased in patients with EGERD ( P = 0.01) and decreased with topical treatment ( P = 0.0025), significantly. HLA-DR, IL8, and NADPH transcripts were significantly increased in the untreated versus controls and comparable significant values were obtained after treatment ( P < 0.05). MUC5AC expression significantly increased with treatment ( P = 0.005). VIP transcripts were significantly higher in EGERD than in controls and decreased with the topical treatment ( P < 0.05). No significant changes were observed in NPY. CONCLUSIONS: We report an increase in prevalence of ocular discomfort in patients with GERD/LPR. The observations of VIP and NPY transcripts demonstrate the potential neurogenic nature of the inflammatory state. Restoration of the ocular surface parameters suggests the potential usefulness of topical alginate therapy.

Inflammation and Dry Eye-like Symptoms as Concomitant Manifestations of Laryngo-Pharyngeal Reflux.

PURPOSE: Laryngopharyngeal reflux (LPR) is a common worldwide disease. LPR symptoms may involve distant organs and tissues including the ocular surface with manifestations of a Dry Eye-like disease. We evaluated the concomitant involvement of the ocular surface in patients with LPR. We also defined the clinical signs and the roles of chemical and neuro-inflammatory mediators in the tears of LPR patients. METHODS: Seventy-seven patients with LPR (mean age 65.8 ± 16.8 SD) and 25 healthy controls (mean age 56.5 ± 16.3 SD) were recruited from the otorhinolaryngology unit. Each subject was evaluated for the presence of concomitant ocular surface disease through clinical examination, including the measurement of tear break-up time (TBUT) and the Ocular Surface Disease Index (OSDI) questionnaire. Tears and conjunctival imprints were collected. The presence of pepsin in tears was detected by ELISA. HLA-DR in conjunctival imprints were imaged by immunofluorescence microscopy. RT-PCR quantified conjunctival mRNA transcripts of HLA-DR, IL-8, MUC5AC, NADPH, VIP, and NPY. RESULTS: Patients with LPR had significantly increased OSDI and reduced TBUT scores compared to control subjects (p < 0.05 each). Pepsin was detected in 51% of patient tears while it was not measurable in the controls (p < 0.01). Immunoreactivity for HLA-DR in the conjunctival impressions was greater than for the controls with an increased mRNA expression (p < 0.05). mRNA transcripts for IL-8, NADPH, and VIP were significantly increased in LPR patients (p < 0.05 each), but neither MUC5AC nor NPY was different from controls. CONCLUSIONS: LPR can adversely affect the ocular surface, leading to moderate signs and symptoms of dry eye. This study provides evidence that the presence of pepsin, HLA-DR immunoreactivity, and increased mRNA expression of neuro-inflammatory markers in the tears and conjunctival imprints of LPR patients suggests a potential link between LPR inflammation and ocular surface disease.

Hypoglossal nerve stimulation long-term clinical outcomes: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis for studies evaluating hypoglossal nerve stimulation (HNS) clinical outcomes in the treatment of moderate to severe obstructive sleep apnea (OSA). METHODS: Two authors conducted a literature search to identify prospective studies in PubMed/MEDLINE, Google Scholar, and Cochrane Library databases. The last search was performed on November 17, 2018. RESULTS: A total of 350 patients (median age 54.3 (IQR 53-56.25) years, BMI 29.8 (IQR 28.8-31.6) kg/m2) from 12 studies were included. The procedure has obtained a surgical success rate of 72.4% (Inspire), 76.9% (ImThera), 55% (Apnex) at 12 months, and 75% (Inspire) at 60-month follow-up. At 12 months, the apnea-hypopnea index (AHI) mean differences was - 17.50 (Inspire; 95% CI: - 20.01 to - 14.98, P < 0.001), - 24.20 (ImThera; 95% CI: - 37.39 to 11.01, P < 0.001), and - 20.10 (Apnex; 95% CI: - 29.62 to - 10.58, P < 0.001). The AHI mean reduction after 5 years was - 18.00 (Inspire, - 22.38 to - 13.62, P < 0.001). The Epworth sleepiness scale (ESS) mean reduction was - 5.27 (Inspire), - 2.90 (ImThera), and - 4.20 (Apnex) at 12 months and - 4.40 (Inspire) at 60 months, respectively. Only 6% of patients reported serious device-related adverse events after 1- and 5-year follow-up. CONCLUSION: HNS has obtained a high surgical success rate with reasonable long-term complication rate related to the device implanted. The procedure represents an effective and safe surgical treatment for moderate-severe OSA in selected adult patients who had difficulty accepting or adhering to CPAP treatment.

Excessive daytime sleepiness is associated to the development of swallowing impairment in a cohort of early stage drug naïve Parkinson's disease patients.

OBJECTIVE: The aim of the present study was to investigate the potential predictors of subjectively reported swallowing impairment in a cohort of early-stage and drug naïve Parkinson's disease patients. METHODS: A retrospective analysis of the Parkinson Progression Markers Initiative (PPMI) data was conducted. PD patients with score ≥ 1 on MDS-UPDRS "item 2.3" and on SCOPA-AUT "question 1" were classified as "dysphagic" and were compared with "non-dysphagic" patients at baseline. After excluding baseline dysphagic subjects, we assessed the predictors of the development of dysphagia in the third year of follow-up. RESULTS: The baseline prevalence of dysphagia in PD was 10.4%, growing as high as 19.1% within year 3. Compared to PD subjects not complaining swallowing difficulties, dysphagic patients had significantly higher scores on REM sleep behavior questionnaire, Epworth sleepiness scale (ESS), geriatric depression scale and MDS-UPDRS I (p < .01), significantly lower caudate [123I]FP-CIT uptake parameters and BMI, and mild cognitive changes at symbol digit modalities (p < .01). In the longitudinal analysis of non-dysphagic patients, 14.6% developed dysphagic symptoms at year 3. Excessive daytime sleepiness estimated through ESS was strongly related to the development of swallowing impairment at year 3 in the univariate (odds ratio 3.2, p < .001) and multivariate regression model (odds ratio 2.5, p = .01). CONCLUSIONS: Early-stage PD patients often report swallowing difficulties. We found a close relationship between excessive daytime sleepiness and the development of swallowing impairment over three years of follow-up of de novo patients.