Treatment adherence to olfactory training: a real-world observational study.

BACKGROUND: Olfactory training (OT) is considered an effective intervention for most causes of smell loss and is recommended as a long-term treatment. However, the treatment adherence of OT remains unclear. This study aims to identify the frequency and causalities for lack of adherence to OT. METHODS: In this prospective study, 53 patients previously diagnosed with olfactory dysfunction (OD), who were recommended to perform OT, were enrolled. Patients underwent olfactory testing using Sniffin' Sticks for threshold, discrimination, and identification (TDI) and a subjective numeric rating scale (NRS) at a baseline and follow-up visit. In addition, patients answered a six-item treatment adherence questionnaire. The primary outcome measures were clinically relevant improvements according to the TDI (>=5.5) and NRS (>=5.5) scores. RESULTS: Out of 53 patients, 45 performed OT. Among patients who performed OT, 31% discontinued the use of OT on their own due to a self-perceived improvement, while 51% discontinued use due to lack of improvements in olfaction. In these patients, the average duration of OT use was five months. After controlling for baseline duration of OD, baseline TDI score and smell loss aetiologies, discontinuing OT due to a lack of self-perceived improvement remained significantly associated with worse TDI and NRS outcomes at follow-up. CONCLUSIONS: Our data show that therapeutical adherence to OT is low, regardless of patients' perception of olfactory function. Olfactory improvement leads to decreased training due to satisfaction, while lack of improvement leads to non-adherence based on disappointing subjective outcome. Patients should be advised to perform OT consistently.

Overall symptom severity as a patient-reported outcome measure for chronic rhinosinusitis: what it reflects and how to measure it.

BACKGROUND: The objective of this study was to identify how - and to what extent - overall symptom severity (OSS) score reflects individual chronic rhinosinusitis (CRS) symptoms and whether it can be measured using alternatives to the standard visual analog scale (VAS). METHODS: CRS patients from four sites across three continents rated their OSS scores, severities of nasal obstruction, nasal drainage, decreased sense of smell, facial pain/pressure and sleep disturbance using a standard VAS, VAS with labeled tick marks at every 1 centimeter, and by writing down their OSS on a scale of 0 - 100 (which was divided by 10), all of which lead to severity scores ranging from 0 - 10 in 0.1 intervals. Quality of life was measured using the SNOT-22 and EQ-5D VAS. RESULTS: In 311 CRS patients, OSS score was significantly correlated with SNOT-22 and EQ-5D VAS. OSS score was most greatly associated with the mean of all individual symptom severity scores. From individual CRS symptoms, OSS was most greatly associated with nasal obstruction followed by nasal drainage and facial pain/pressure severities. These results held true for participants with and without nasal polyps. Measurement of OSS and individual symptom severity scores using a standard VAS, tick-marked VAS, and write-in option had near-perfect consistency. CONCLUSIONS: We demonstrate for the first time that OSS largely reflects the mean of individual CRS symptom severities, although OSS is=== most weighted by nasal obstruction severity. OSS and individual symptom severity scores can be measured using a standard VAS, tick-marked VAS or write-in prompt with near-perfect consistency.

Extreme weather conditions influence the frequency of epistaxis-related emergency room visits.

BACKGROUND: Climate change has been associated with an increase in extreme weather conditions. The aim of this study was to identify environmental factors and the effect of extreme weather events (95th percentile) on the risk for epistaxis-related emergency room visits (EV). METHODS: A total of 2179 epistaxis-related EVs were identified between 2015 and 2018. A distributed lag non-linear model was fitted to investigate the relationship between extreme weather conditions and the total number of epistaxis-related EVs per day. Cumulative relative risk (cRR) is defined as the cumulated daily risk of EV for epistaxis within a stated period after an extreme weather condition compared to the risk of EV at the median value of that weather condition. RESULTS: At a mean daily temperature of 27°C (P95), cRR for epistaxis-related EV was 2.00. At a relative humidity of 39% (P5), cRR was highest on day 3 at 1.59, while extremely high humidity (92%, P99) led to a decreased cRR of 0.7 on day 1. Intense precipitation of 24mm (P99) reduced the cRR on day 3 to 0.38. For prolonged extreme conditions over three days, extremely low wind speed, as well as both high and low atmospheric pressure events, diminished cRR. CONCLUSIONS: Extreme temperatures, relative humidity, and precipitation, as well as extended periods of extreme wind speeds and atmospheric pressure, significantly impact cRR for epistaxis-related EVs.

Efficacy and safety of switching between biologics in chronic rhinosinusitis with nasal polyps or N-ERD.

BACKGROUND AND OBJECTIVE: The effectiveness of biologics in chronic rhinosinusitis with nasal polyps (CRSwNP) is well-established. However, real-world experience on the effectiveness of transitioning between two monoclonal antibodies is scarce. Therefore, we aimed to analyze the safety and efficacy of antibody switching in treatment of chronic rhinosinusitis. METHODS: All patients with CRSwNP or nonsteroidal anti-inflammatory drugs-exacerbated respiratory disease (N-ERD) requiring a switch between biologics were retrospectively studied. Analysis included changes in polyp size, quality of life parameters, asthma control, and side effects. RESULTS: Out of 195 patients treated with biologics for CRSwNP or N-ERD in our center, 23 (11.8%) required transition to a different monoclonal antibody. The majority switched from omalizumab to dupilumab (17/23, 73.9%), mostly due to inadequate symptom control. Nine out of these 17 patients (52.9%) were switched without a washout period. All patients showed significant improvement in nasal polyp score, asthma control test and sino-nasal outcome test-22 after changing to dupilumab. Keratoconjunctivitis sicca was the side-effect (4.3%) reported after the switch from omalizumab to dupilumab, which lead to termination of therapy in one patient. Due to limited sample size, other antibody transitions were reported in a descriptive manner. CONCLUSION: The transition to dupilumab is an effective option in patients with inadequate treatment response or side-effects of omalizumab in nasal polyposis. Our preliminary results indicate that a wash-out period may not be necessary when switching between biologics, however, these findings require further investigations. Other monoclonal antibody transitions also show promising results, but warrant validations in larger cohorts due to small patient samples in our study.

[Clinical features and CT findings of fibrosing mediastinitis associated pulmonary hypertension].

Objective: To investigate the clinical features and CT findings of pulmonary hypertension (PH) in patients with fibrosing mediastinitis (FM). Methods: Thirteen patients with FM diagnosed between September 2015 and June 2022 were studied retrospectively, including patients with PH (FM-PH group) and patients without PH (FM group) confirmed on right heart catheterization. The t test of two independent samples, Mann-Whitney U rank sum and Fisher's test were used to compare the general information, symptoms, laboratory examination, right ventricular and pulmonary artery measurement data and pulmonary artery CT findings between the two groups, respectively. Results: Compared with the 7 FM patients aged 28-79 (60.00±17.69) years, the 6 patients in the FM-PH group, aged from 60 to 82 (68.83±8.35) years, had more peripheral edema, lower percentage of PaO2, wider inner diameters of pulmonary artery and right ventricle, a higher ratio of right ventricle and left ventricular transverse diameter, faster tricuspid regurgitation velocity and higher estimated systolic pulmonary artery pressure (P<0.05). There were no differences in BNP levels and tricuspid annular plane systolic excursion between groups (P>0.05). Of the 6 patients with PH, 5 had precapillary PH and 1 had mixed PH. Except that the pulmonary vascular resistance in patients of the FM-PH group was significantly higher than that in the FM group (P<0.05), there were no significant differences in cardiac output, mixed venous oxygen saturation and pulmonary capillary wedge pressure between the two groups. CT pulmonary angiography (CTPA) showed pulmonary artery and vein stenosis. Patients in the FM-PH group had more severe stenosis and occlusion of pulmonary artery and pulmonary vein (P<0.05), and more involvement of multiple pulmonary veins (P<0.05). Conclusions: The clinical manifestation of FM complicated with PH is related to the degree of involvement of pulmonary artery, vein and airway. It is recommended that the disease be evaluated in combination with multiple parameters such as clinical manifestations, cardiac ultrasound, right cardiac catheter and CTPA.

Individual importance of olfaction decreases with duration of smell loss.

BACKGROUND: The personal importance of a lost neurologic - motor or sensory - function in several conditions has been shown to decrease as the afflicted patient becomes accustomed to not having that function. It is unknown how the importance of olfaction changes with duration of olfactory dysfunction (OD). The aim of this study was to evaluate the association between duration of smell loss and individual significance of olfaction, and whether this relationship would be modulated by other factors, such as etiology of smell loss. METHODS: This is a retrospective study including a total 163 subjects with different degrees of olfactory function. Individual significance of olfaction was measured using the Importance of Olfaction Questionnaire (IOQ). Demographics, olfactory function, duration and etiology of OD were evaluated. Group comparisons, bivariate correlations, analyses of variance and multivariate linear regression were applied to detect differences and associations with the outcome measure of IOQ. RESULTS: A significant negative correlation was found between duration of OD and the IOQ. Other important findings include a significantly higher IOQ in patients with posttraumatic- compared to idiopathic OD and in patients with higher aggravation scores compared to the lower aggravation group. Multivariate regression analysis further confirmed that duration of smell loss was independently associated with IOQ. CONCLUSIONS: The duration of smell loss is negatively correlated with the individual importance of olfaction, suggesting that patients develop coping mechanisms for adjusting to OD.

Multi-institutional minimal clinically important difference of the 22-item Sinonasal Outcome Test in medically managed chronic rhinosinusitis.

BACKGROUND: With a rapid proliferation of clinical trials to study novel medical treatments for CRS, the objective of this study was to study the minimal clinically important difference (MCID) of the 22-item Sinonasal Outcome Test (SNOT-22) in medically-managed CRS patients. METHODS: A total of 183 medically-treated CRS patients were recruited. All patients completed a SNOT-22 at enrollment and subsequent follow up visit. Distribution and anchor-based methods were used for MCID calculation. These data were combined with data from a previously published study on SNOT-22 MCID in 247 medically managed CRS patients to determine a final recommended MCID value using the combined cohort of 430 patients. RESULTS: In our cohort, distribution- and anchor-based methods -"using both sinus-specific and general health anchors-"provided greatest support for a 12-point SNOT-22 MCID, which had approximately 55% sensitivity but 81% specificity for detecting patients explicitly reporting improvement in their sinus symptoms and general health. In the combined cohort of 430 patients, we also found greatest support for a 12-point SNOT-22 MCID, which had approximately 57% sensitivity and 81% specificity for detecting patients explicitly reporting improvement in their sinus symptoms and general health. We also find evidence that the MCID value may be higher in CRS patients without nasal polyps compared to those with nasal polyps. CONCLUSIONS: Our results - which include data from patients from two different institutions and regions - confirm a SNOT-22 MCID of 12 in medically managed CRS patients. The SNOT-22 MCID was specific but not sensitive for identifying CRS patients experiencing improvement in symptoms or general health.

Factors associated with relevant olfactory recovery after olfactory training: a retrospective study including 601 participants.

OBJECTIVE: Olfactory training (OT) represents a therapeutic option for multiple etiologies of olfactory dysfunction (OD) that also benefits normosmic subjects. In this retrospective study, we report the effectiveness of OT and factors associated with relevant changes in olfactory function (OF) in large groups of normosmic participants and patients with OD, including a control group that performed no training. METHODS: This was a retrospective pooled analysis including 2 treatment cohorts of 8 previously published studies. Adult participants that either presented with the major complaint of quantitative OD or normosmic volunteers were recruited at various ENT clinics and received OT or no training. The outcome was based on changes in objective olfactory test scores after OT. RESULTS: A total of 601 patients with OD or normosmic subjects were included. OT was more effective compared to no training. No interaction was found between OT and OF. In multivariate analysis, higher baseline OF (adjusted odds ratio, aOR, 0.93) and posttraumatic (aOR, 0.29) or idiopathic OD (aOR, 0.18) compared to postinfectious causes were significantly associated with lower odds of relevant improvements in patients with OD receiving OT. Subgroup analysis of normosmic participants receiving OT further revealed a significant association of lower age and baseline olfactory function with improvements of overall OF. CONCLUSIONS: This study demonstrated that OT was more effective than no training in patients with various causes of OD. Additionally, baseline olfactory performance and etiology of OD were identified as important factors associated with relevant improvements after OT.

Plasma VEGF - a candidate biomarker for response to treatment with bevacizumab in HHT patients.

BACKGROUND: Recurrent epistaxis is the principal symptom of hereditary hemorrhagic telangiectasia (HHT). Currently, there is no standard therapy for this condition. Bevacizumab (anti-VEGF) treatment has been under intense investigation but treatment effects vary greatly between individuals. There are currently no markers to predict anti-VEGF therapeutic response in HHT patients. METHODS: We evaluated plasma VEGF levels in 13 HHT patients and correlated values with i) degree of epistaxis, measured by visual analog scale (VAS), epistaxis severity score (ESS), and patient bleeding diaries ii) the prevalence of extranasal manifestations, iii) the HHT subtype and iv) the treatment response to intranasal submucosal bevacizumab. RESULTS: Plasma VEGF was elevated in all 13 HHT patients compared to reference levels and showed a moderate correlation with VAS and duration of moderate bleeding events. In patients treated with intranasal submucosal bevacizumab plasma VEGF levels showed a strong correlation with the degree of reduction of mild bleeding events and VAS. CONCLUSIONS: The role of plasma VEGF as a potential predictive biomarker for therapeutic response to bevacizumab treatment warrants further investigation in larger prospective studies.

Factors associated with relevant olfactory recovery after olfactory training: a retrospective study including 601 participants.

BACKGROUND: Olfactory training (OT) represents a therapeutic option for multiple etiologies of olfactory dysfunction (OD) that also benefits normosmic subjects. In this retrospective study, we report the effectiveness of OT and factors associated with relevant changes in olfactory function (OF) in large groups of normosmic participants and patients with OD, including a control group that performed no training. METHODS: This was a retrospective pooled analysis including 2 treatment cohorts of 8 previously published studies. Adult partici- pants that either presented with the major complaint of quantitative OD or normosmic volunteers were recruited at various ENT clinics and received OT or no training. The outcome was based on changes in objective olfactory test scores after OT. RESULTS: A total of 601 patients with OD or normosmic subjects were included. OT was more effective compared to no training. No interaction was found between OT and OF. In multivariate analysis, higher baseline OF (adjusted odds ratio, aOR, 0.93) and posttraumatic (aOR, 0.29) or idiopathic OD (aOR, 0.18) compared to postinfectious causes were significantly associated with lower odds of relevant improvements in patients with OD receiving OT. Subgroup analysis of normosmic participants receiving OT further revealed a significant association of age and baseline olfactory function with improvements of overall OF. CONCLUSIONS: This study demonstrated that OT was more effective than no training in patients with various causes of OD. Additi- onally, baseline olfactory performance and etiology of OD were identified as important factors associated with relevant improve- ments after OT.

Clinicopathological features and prognosis of esophageal squamous cell carcinoma in young patients.

Esophageal squamous cell carcinoma (ESCC) in the young patients is comparatively rare and has not been well studied. We analyzed the clinical and survival data of 127 ESCC patients <40 years at a single high-volume center and compared with those of 4109 ESCC patients ≥40 years who underwent surgery within the same period in this study. The average age was 36.5 ± 0.2 years for the young patient group, with the youngest aged 26 years. Young patients had a higher rate of family history, longer tumors, and a more advanced pT category than their older counterparts. Moreover, more patients in the young group underwent incomplete resection (19.7% vs. 8.9%, P < 0.001) and adjuvant therapy (40.9% vs. 30.8%, P = 0.015). The overall survival (OS) and cancer-specific survival (CSS) between patients <40 years and patients ≥40 years were not significant in the entire group. In the subgroup analysis, the OS and CSS rates for patients <40 years were significantly worse than patients ≥40 years in subgroups of pTNM stage III and incomplete resections. In conclusions, young patients with ESCC were more likely to have family history and present with advanced disease. The survival for young patients with ESCC was poorer than their older counterparts in patients with later stage diseases.

Langerhans cell sarcoma: a case report and review of the literature.

We present the case of a 62-year-old male patient with a three-month history of pain in the left shoulder. Magnetic resonance imaging of the left scapula showed an osteo-destructive lesion. H and E stained sections revealed a Langerhans cell sarcoma, and immunohistochemistry was performed additionally; CD68, CD163, CD14, fascin, HLA-DR, lysozyme, S100 CD1a and langerin showed a positive reaction, while CD20, CD30, CD34, CD31, pan-cytokeratin, AE/1AE3, SMA, desmin, EMA, ERG, INI-1, CD21, CD4, PLAP, MPO and CD117c were negative. We suggested palliative treatment with chemotherapy and radiation. The patient refused any treatment and died 2 weeks later.

Treatment and prognosis of limited disease primary small cell carcinoma of esophagus.

Primary small cell carcinoma of esophagus (SCCE) is a relatively rare and highly aggressive tumor characterized by early dissemination and poor prognosis. The optimal treatment has not yet been established, and the role of surgery has remained controversial. Most of the limited diseases were treated conventionally by surgery, but the five-year survival rate was still very low. This retrospective study was designed to investigate the clinical characteristics, treatment, and prognostic factors of limited disease SCCE. Clinical data of 40 SCCE patients with clinically limited disease who received transthoracic esophagectomy with lymphadenectomy at the Cancer Hospital of Shantou University Medical College from November 1990 to December 2009 were reviewed to summarize the clinical characteristics and treatment impacted on the survival. Twenty-five cases of the 40 patients were treated with surgery alone, eight cases were treated with surgery + postoperative chemotherapy, four cases were treated with surgery + postoperative radiotherapy, and the other three were treated with surgery + postoperative radiochemotherapy. The Kaplan-Meier and log-rank methods were used to estimate and compare survival rates. Cox's hazard regression model was used to identify the prognostic factors with the entry factors of gender, age (≤ 60 years versus > 60 years), length of the primary lesion (≤ 5 cm versus > 5 cm), location of the primary lesion, macroscopic tumor type, pT, pN, pTNM stage, operation (radical/palliative), and chemotherapy (yes/no). The mean follow-up duration of this series was 24.7 months (1-121 months). Thirty-four patients died of the disease during the follow-up, five were still alive, and one was lost of follow-up. The median survival time of the 40 patients was 13.0 months (95% confidence interval 4.7-21.3), and the 6-, 12-, 24-, 36-, and 60-month overall survival rates (OS) were 77.5%, 56.4%, 28.9%, 23.7%, 10.5%, respectively. In univariate analysis, age (≤ 60 years versus >60 years) (P=0.049), operation (radical/palliative) (P=0.008), and chemotherapy (yes/no) (P= 0.013) significantly influenced the OS of the SCCE patients. In multivariate analysis, operation (P=0.015) and chemotherapy (P=0.031) were independent prognostic factors. The patients who received radical surgery and postoperative chemotherapy had relatively better survival. Surgical resection combined with chemotherapy should be recommended to patients with limited disease SCCE.

Subunit stoichiometry of cyclic nucleotide-gated channels and effects of subunit order on channel function.

Cyclic nucleotide-gated (CNG) ion channels are multimeric structures containing at least two subunits. However, the total number of subunits per functional channel is unknown. To determine the subunit stoichiometry of CNG ion channels, we have coexpressed the 30 pS conductance bovine retinal channel (RET) with an 85 pS conductance chimeric retinal channel containing the catfish olfactory channel P region (RO133). When RO133 and RET monomers are coexpressed, channels with four distinct intermediate conductances are observed. Dimer constructs reveal that two of these conductance levels arise from channels with the same subunit composition (2 RO133:2 RET) but distinct subunit order (like subunits adjacent to each other versus like subunits across from each other). Thus, the data demonstrate that cyclic nucleotide-gated ion channels are tetrameric like the related voltage-gated potassium ion channels; the order of subunits affects the conductance of the channel; and the channel has 4-fold symmetry in which four asymmetric subunits assemble head to tail around a central axis.

Constraining ligand-binding site stoichiometry suggests that a cyclic nucleotide-gated channel is composed of two functional dimers.

Cyclic nucleotide-gated ion channels are composed of four pore-forming subunits. Binding of cyclic nucleotide to a site in the intracellular carboxyl terminus of each subunit leads to channel activation. Since there are four subunits, four binding events are possible. In this study, we investigate the effects of individual binding events on activation by studying channels containing one, two, three, or four functional binding sites. The binding of a single ligand significantly increases opening, although four ligands are required for full activation. The data are inconsistent with models in which the four subunits activate in a single concerted step (Monod-Wyman-Changeux model) or in four independent steps (Hodgkin-Huxley model). Instead, the four subunits may associate and activate as two independent dimers.

Vigabatrin-induced visual dysfunction in Chinese patients with refractory epilepsy.

PURPOSE: Bilateral visual field constriction has been reported following the use of the antiepileptic drug (AED) vigabatrin. The incidence of retinal toxicity is variable and there are limited data in Asian populations. The authors report the results of ophthalmologic examination in Chinese patients taking this drug. METHODS: The authors identified two groups of patients with refractory epilepsy: one group on vigabatrin and another cohort of patients taking other AEDs. The authors recorded the medical history and performed visual acuity testing, intraocular pressure measurement, slit lamp biomicroscopy, and conventional automated perimetry with Humphrey Visual Field Analyzer II in all patients. RESULTS: Eighteen patients--8 men and 10 women--with a mean age of 23.8 years who were taking vigabatrin were reviewed. Length of treatment with this drug ranged from 13 months to 5 years and the mean daily dosage was 1581 mg. None of the patients in either group had a history of coexisting optic nerve diseases or other neurotoxic drug use. Twenty of 36 (55.6%) eyes of the vigabatrin users showed significant bilateral visual field defects with 80% showing a concentric pattern, compared with none in the control group. CONCLUSIONS: The authors confirmed a high prevalence of visual field constriction associated with vigabatrin in Chinese patients. The use of alternative novel techniques such as measurement of the retinal nerve fibre layer thickness and perimetry may detect early retinal damage and result in even higher incidences. Visual field monitoring is recommended in patients who continue to take this drug.

Safety enhanced photodynamic therapy with half dose verteporfin for chronic central serous chorioretinopathy: a short term pilot study.

AIM: To evaluate short term safety of an enhanced photodynamic therapy (PDT) protocol with half dose verteporfin for treating chronic central serous chorioretinopathy (CSC). METHODS: 20 eyes of 18 patients with symptomatic chronic CSC underwent PDT using 3 mg/m2 verteporfin. Verteporfin was infused over 8 minutes followed by indocyanine green angiography guided laser application 2 minutes later. Serial optical coherence tomography (OCT) and multifocal electroretinography (mfERG) recordings were performed before PDT, at 4 days, 2 weeks, and 1 month after PDT. The best corrected visual acuity (BCVA), OCT central retinal thickness, and mean mfERG response amplitudes and peak latencies were compared longitudinally. Subgroup analysis was further performed for eyes with or without pigment epithelial detachment (PED). RESULTS: At 1 month after PDT, the median BCVA improved from 20/40 to 20/30 (p = 0.001). The mean central retinal thickness also reduced from 276 microm to 158 microm (p < 0.001) and 17 (85%) eyes had complete resolution of serous retinal detachment and/or PED. MfERG showed no significant changes in the mean N1 and P1 response amplitude and latency for all eyes. Subgroup analysis demonstrated that eyes without PED had a significant increase in the mean central mfERG P1 response amplitude with reduction in P1 peak latency at 1 month post-PDT. For eyes with PED, transient reduction in the mean central P1 response amplitude was observed at 4 days post-PDT. CONCLUSIONS: The modified safety enhanced PDT protocol with half dose verteporfin appeared to be a beneficial treatment option for patients with chronic CSC, especially in eyes without serous PED. Further controlled study is warranted to demonstrate the long term safety and efficacy of this treatment option.

Combined photodynamic therapy and intravitreal triamcinolone injection for the treatment of subfoveal choroidal neovascularisation in age related macular degeneration: a comparative study.

AIM: To evaluate the outcomes of combined intravitreal triamcinolone (IVTA) and photodynamic therapy (PDT) with verteporfin in the treatment of subfoveal choroidal neovascularisation (CNV) caused by age related macular degeneration (AMD). METHODS: 48 eyes from 48 patients with subfoveal CNV caused by AMD were prospective recruited, with 24 eyes treated with combined PDT with IVTA and compared with a control group of 24 eyes which received PDT monotherapy. In the combined treatment group, IVTA was performed immediately after PDT as an outpatient procedure. The mean number of treatments, mean logMAR best corrected visual acuity (BCVA), mean line of visual acuity changes, and proportion of patients without moderate visual loss at 1 year were compared between the combined and monotherapy groups. RESULTS: At 1 year the logMAR BCVA for the PDT with IVTA group changed from 0.88 to 0.95 (p = 0.32 compared with baseline), whereas the logMAR BCVA for the monotherapy group reduced from 0.74 to 1.09 (p<0.001 compared with baseline). A significantly higher proportion of patients who had PDT with IVTA did not develop moderate visual loss at 1 year compared with the monotherapy group (70.8% and 33.3% respectively, p = 0.009). Eyes which had combined treatment had significantly fewer lines lost compared with monotherapy alone (0.7 and 3.5 lines respectively, p = 0.015). Subgroup analysis showed that PDT with IVTA is effective in preventing visual loss in both predominately classic and occult CNV groups. The mean number of treatments for the combined and monotherapy groups was 1.5 and 1.96 respectively (p = 0.076). CONCLUSIONS: Combined PDT with IVTA appeared more effective statistically at 12 months for stabilisation of vision (<3 logMAR lines change) compared with PDT monotherapy. Further randomised control trials might be justified to conclude the efficacy of PDT with IVTA.

Choroidal neovascularisation in pathological myopia: an update in management.

Choroidal neovascularisation (CNV) secondary to pathological myopia is an important cause of significant visual impairment in young and middle aged adults globally and is particularly prevalent in Asian populations. In the past few years, there have been rapid advancements in the different treatments for myopic CNV. The purpose of this perspective is to give an overview of the natural history of myopic CNV and the various treatment options including laser photocoagulation, photodynamic therapy, sub-macular surgery, and macular translocation surgery. Future directions in the management of myopic CNV are also discussed.

Inhibitory effect of circulating insulin on glucagon secretion during hypoglycemia in type I diabetic patients.

OBJECTIVE: To clarify whether the circulating insulin level influences hormonal responses, glucagon secretion in particular, during hypoglycemia in patients with insulin-dependent (type I) diabetes. RESEARCH DESIGN AND METHODS: Nine type I diabetic patients were studied. During two separate experiments, hypoglycemia was induced by low-dose (244 pmol.kg-1.h-1) and high-dose (1034 pmol.kg-1.h-1) intravenous insulin infusions for 180 min in each case. The arterial blood glucose level was directly monitored every 1.5 min, and glucose was infused in the high-dose test to clamp the arterial blood glucose level to be identical as in the low-dose test. RESULTS: Despite the fact that the plasma insulin level was four times higher in the high-dose than in the low-dose test (740 +/- 50 vs. 180 +/- 14 pM), a close to identical arterial hypoglycemia of approximately 3.3 mM was obtained in the two experiments. During hypoglycemia, a significant rise of the plasma glucagon level was found only in the low-dose test (188 +/- 29 vs. 237 +/- 37 ng/L, P less than 0.05), and the incremental area under the glucagon curve was significantly greater in the low-dose than in the high-dose test (140 +/- 19 vs. -22.7 +/- 34 ng/L.h-1, P less than 0.005). The responses of plasma epinephrine, norepinephrine, growth hormone, pancreatic polypeptide, and somatostatin were similar in both tests and, consequently, were not significantly modified by the circulating insulin level. CONCLUSIONS: This study demonstrates that, in type I diabetic patients, the glucagon response to hypoglycemia is suppressed by a high level of circulating insulin within the physiological range. Our findings may help to explain the impairment of glucagon secretion during hypoglycemia frequently seen in these patients.