Acute Myopic Shift after a Single Dose of Acetazolamide: A Case Report and Review of the Literature.

We report the case of a 32-year-old male who presented with an acute myopic shift as a result of uveal effusion following a single administration of 250 mg acetazolamide. The drug was discontinued and following cycloplegia and topical steroid therapy, we observed progressive deepening of the anterior chamber, reopening of the iridocorneal angle, and complete resolution of the myopic shift after 5 days. A literature review since 1956 identified 23 cases, including ours, which developed a myopic shift after a median time of 24 h (3 - 24) following a median dose of 500 mg (125 - 1000) acetazolamide, with about a third complicated by angle closure ocular hypertension. This presumed idiosyncratic reaction can occur without prior drug exposure and independent of the phakic status. Treatment options include systematic drug withdrawal associated with cycloplegia, anti-glaucomatous agents, and/or corticosteroids. Full recovery is achieved within about 5 days (2 - 14). Given the widespread use of acetazolamide, awareness of this idiosyncratic reaction is crucial to avoid complications of acute angle-closure glaucoma.

The regional pattern of abnormal cerebrovascular reactivity in HIV-infected, virally suppressed women.

The purpose of this study was to assess whole brain and regional patterns of cerebrovascular reactivity (CVR) abnormalities in HIV-infected women using quantitative whole brain arterial spin labeling (ASL). We hypothesized that HIV-infected women would demonstrate decreased regional brain CVR despite viral suppression. This cross-sectional study recruited subjects from the Bay Area Women's Interagency Health Study (WIHS)-a cohort study designed to investigate the progression of HIV disease in women. In addition to conventional noncontrast cerebral MRI sequences, perfusion imaging was performed before and after the administration of intravenous acetazolamide. CVR was measured by comparing quantitative ASL brain perfusion before and after administration of intravenous acetazolamide. In order to validate and corroborate ASL-based whole brain and regional perfusion, phase-contrast (PC) imaging was also performed through the major neck vessels. FLAIR and susceptibility weighted sequences were performed to assess for white matter injury and microbleeds, respectively. Ten HIV-infected women and seven uninfected, age-matched controls were evaluated. Significant group differences were present in whole brain and regional CVR between HIV-infected and uninfected women. These regional differences were significant in the frontal lobe and basal ganglia. CVR measurements were not significantly impacted by the degree of white matter signal abnormality or presence of microbleeds. Despite complete viral suppression, dysfunction of the neurovascular unit persists in the HIV population. Given the lack of association between CVR and traditional imaging markers of small vessel disease, CVR quantification may provide an early biomarker of pre-morbid vascular disease.

Morbidity Among Athletes Presenting for Medical Care During 3 Iterations of an Ultratrail Race in the Himalayas.

INTRODUCTION: Although ultratrail races are increasing in popularity, there is a dearth of data regarding illnesses and medical care at these events. Data about injuries and illnesses for races taking place in the Himalayas, where the nearest medical facility can be hundreds of miles away, are even harder to find. This study aimed to describe the injuries and illnesses befalling the participants of a 7-stage 212 km (132 mi) trail race at high altitude. METHODS: Ethical approval was obtained from Nepal Research Health Council. A retrospective study of the record of medical encounters among the 100 participants competing in the Manaslu trail race in Nepal from 2014 to 2016 was performed. Diagnoses were classified into various categories. Informed consent was taken from all participants. RESULTS: Acute diarrhea was the most common ailment reported among the participants (18%), followed closely by musculoskeletal problems (17%). Altitude illness made up 6% of care provided. Approximately 35% of the athletes were using acetazolamide as prophylaxis for high altitude illnesses. The 1 case needing evacuation in the 3 iterations was high altitude pulmonary edema. CONCLUSIONS: Ultratrail races at high altitude pose a challenge in terms of provision of medical care in a remote setting with limited resources. However, most of the illnesses are minor in nature and easily managed by the race doctor. Knowledge of common illnesses among travelers to the area can help aid in preparation and provision of proper care, especially in remote settings with limited resources.

Hemodynamic provocation with acetazolamide shows impaired cerebrovascular reserve in adults with sickle cell disease.

Sickle cell disease is characterized by chronic hemolytic anemia and vascular inflammation, which can diminish the vasodilatory capacity of the small resistance arteries, making them less adept at regulating cerebral blood flow. Autoregulation maintains adequate oxygen delivery, but when vasodilation is maximized, the low arterial oxygen content can lead to ischemia and silent cerebral infarcts. We used magnetic resonance imaging of cerebral blood flow to quantify whole-brain cerebrovascular reserve in 36 adult patients with sickle cell disease (mean age, 31.9±11.3 years) and 11 healthy controls (mean age, 37.4±15.4 years), and we used high-resolution 3D FLAIR magnetic resonance imaging to determine the prevalence of silent cerebral infarcts. Cerebrovascular reserve was calculated as the percentage change in cerebral blood flow after a hemodynamic challenge with acetazolamide. Co-registered lesion maps were used to demonstrate prevalent locations for silent cerebral infarcts. Cerebral blood flow was elevated in patients with sickle cell disease compared to controls (median [interquartile range]: 82.8 [20.1] vs 51.3 [4.8] mL/100g/min, P<0.001). Cerebral blood flow was inversely associated with age, hemoglobin, and fetal hemoglobin, and correlated positively with bilirubin, and LDH, indicating that cerebral blood flow may reflect surrogates of hemolytic rate. Cerebrovascular reserve in sickle cell disease was decreased by half compared to controls (34.1 [33.4] vs 69.5 [32.4] %, P<0.001) and was associated with hemoglobin and erythrocyte count indicating anemia-induced hemodynamic adaptations. In total, 29/36 patients (81%) and 5/11 controls (45%) had silent cerebral infarcts (median volume of 0.34 vs 0.02 mL, P=0.03). Lesions were preferentially located in the borderzone. In conclusion, patients with sickle cell disease have a globally reduced cerebrovascular reserve as determined by arterial spin labeling with acetazolamide and reflects anemia-induced impaired vascular function in sickle cell disease. This study was registered at clinicaltrials.gov identifier 02824406.

Human bronchial carcinoid tumor initiating cells are targeted by the combination of acetazolamide and sulforaphane.

BACKGROUND: Bronchial carcinoids are neuroendocrine tumors that present as typical (TC) and atypical (AC) variants, the latter being more aggressive, invasive and metastatic. Studies of tumor initiating cell (TIC) biology in bronchial carcinoids has been hindered by the lack of appropriate in-vitro and xenograft models representing the bronchial carcinoid phenotype and behavior. METHODS: Bronchial carcinoid cell lines (H727, TC and H720, AC) were cultured in serum-free growth factor supplemented medium to form 3D spheroids and serially passaged up to the 3rd generation permitting expansion of the TIC population as verified by expression of stemness markers, clonogenicity in-vitro and tumorigenicity in both subcutaneous and orthotopic (lung) models. Acetazolamide (AZ), sulforaphane (SFN) and the AZ + SFN combination were evaluated for targeting TIC in bronchial carcinoids. RESULTS: Data demonstrate that bronchial carcinoid cell line 3rd generation spheroid cells show increased drug resistance, clonogenicity, and tumorigenic potential compared with the parental cells, suggesting selection and expansion of a TIC fraction. Gene expression and immunolabeling studies demonstrated that the TIC expressed stemness factors Oct-4, Sox-2 and Nanog. In a lung orthotopic model bronchial carcinoid, cell line derived spheroids, and patient tumor derived 3rd generation spheroids when supported by a stroma, showed robust tumor formation. SFN and especially the AZ + SFN combination were effective in inhibiting tumor cell growth, spheroid formation and in reducing tumor formation in immunocompromised mice. CONCLUSIONS: Human bronchial carcinoid tumor cells serially passaged as spheroids contain a higher fraction of TIC exhibiting a stemness phenotype. This TIC population can be effectively targeted by the combination of AZ + SFN. Our work portends clinical relevance and supports the therapeutic use of the novel AZ+ SFN combination that may target the TIC population of bronchial carcinoids.

Acetazolamide as a potent chloride-regaining diuretic: short- and long-term effects, and its pharmacologic role under the 'chloride theory' for heart failure pathophysiology.

According to the "chloride theory" for heart failure (HF) pathophysiology, manipulation of the serum chloride concentration is an important therapeutic target. This study determined the short- and long-term effects of acetazolamide (Diamox), a potential chloride-regaining diuretic, on peripheral blood, serum electrolytes, and renal function. Effects of low-dose Diamox (250-500 mg/day) were evaluated in 30 HF patients for whom Diamox was added as de-novo/add-on decongestion therapy for acutely worsening HF (n = 18) or as modification therapy for serum hypochloremia in stable HF ( < 100 mEq/L; n = 12). Peripheral hematologic tests were performed at baseline, and at short- ( ≤ 10 days) and long-term ( ~ 60 days) time-points. In all 30 study patients of both groups, the serum chloride concentration increased in the short-term and even further over the long-term. The serum potassium concentration constantly decreased throughout the study period. Both the blood urea nitrogen and serum creatinine concentrations increased in the short-term, but returned to baseline levels over the long-term. Responders to Diamox (n = 13; defined by HF resolution and body weight loss ≥ 1 kg) in the decongestion group exhibited reduced serum b-type natriuretic peptide levels and a markedly increased serum chloride concentration, but the hemoglobin/hematocrit and serum creatinine concentrations did not change after treatment. In conclusion, acetazolamide is a potent candidate "chloride-regaining diuretic" for treating HF patients under the "chloride theory". Its effect to enhance the serum chloride concentration occurred within 10 days and persisted for at least ~ 60 days. Plasma volume and renal function were preserved under adequate diuretic treatment with acetazolamide.

RESPONSE OF INFLAMMATORY CYSTOID MACULAR EDEMA TO TREATMENT USING ORAL ACETAZOLAMIDE.

PURPOSE: To determine the treatment effect of oral acetazolamide on refractory inflammatory macular edema. METHODS: A retrospective review of identified patients with uveitic or pseudophakic macular edema treated using acetazolamide between 2007 and 2014. Visual acuity and central macular subfield thickness was determined at baseline and at first follow-up. Baseline optical coherence tomography features were analyzed as predictors of acetazolamide response. RESULTS: Sixteen patients (19 eyes) of 61 screened met all criteria. Mean age was 57.9 years (19.7-81.1). The most common diagnosis was idiopathic uveitis (n = 6, 31.6%). Mean uveitis duration was 4.4 years (0.2-27.5). Average central macular subfield thickness decreased significantly (from 471.8 ± 110.6 µm to 358.3 ± 50.4 µm) (P < 0.0001). Average visual acuity (logarithm of the minimum angle of resolution) improved significantly from 20/54 (0.43 ± 0.25) to 20/37 (0.27 ± 0.16) (P = 0.003). Pretreatment optical coherence tomographies demonstrated intraretinal fluid (n = 19, 100%), subretinal fluid (n = 8, 42.1%), epiretinal membrane (n = 13, 68.3%), and vitreomacular traction (n = 1, 5.2%). No optical coherence tomography characteristic was predictive of a response to therapy. CONCLUSION: There is a significant benefit to vision and central macular subfield thickness after acetazolamide treatment in patients with inflammatory macular edema. In patients with refractory inflammatory macular edema, treatment using acetazolamide can provide anatomical and visual benefit without corticosteroid-related adverse effects.

Reduced Acetazolamide Dosing in Countering Altitude Illness: A Comparison of 62.5 vs 125 mg (the RADICAL Trial).

INTRODUCTION: North American guidelines propose 125 mg acetazolamide twice daily as the recommended prophylactic dose to prevent acute mountain sickness (AMS). To our knowledge, a dose lower than 125 mg twice daily has not been studied. METHODS: We conducted a prospective, double-blind, randomized, noninferiority trial of trekkers to Everest Base Camp in Nepal. Participants received the reduced dose of 62.5 mg twice daily or the standard dose of 125 mg twice daily. Primary outcome was incidence of AMS, and secondary outcomes were severity of AMS and side effects in each group. RESULTS: Seventy-three participants had sufficient data to be included in the analysis. Overall incidence of AMS was 21 of 38 (55.3%) in reduced-dose and 21 of 35 (60.0%) in standard-dose recipients. The daily incidence rate of AMS was 6.7% (95% CI 2.5-10.9) for each individual in the reduced-dose group and 8.9% (95% CI 4.5-13.3) in the standard-dose group. Overall severity of participants' Lake Louise Score was 1.014 in the reduced-dose group and 0.966 in the standard-dose group (95% CI 0.885-1.144). Side effects were similar between the groups. CONCLUSIONS: The reduced dose of acetazolamide at 62.5 mg twice daily was noninferior to the currently recommended dose of 125 mg twice daily for the prevention of AMS. Low incidence of AMS in the study population may have limited the ability to differentiate the treatment effects. Further research with more participants with greater rates of AMS would further elucidate this reduced dosage for preventing altitude illness.

Comparative Oral Drug Classification Systems: Acetazolamide, Azithromycin, Clopidogrel, and Efavirenz Case Studies.

Biopharmaceutics classification systems based on the properties of solubility and permeability or the extension of metabolism are very important tools in the early stages of the development and regulatory stages of new products. However, until now, there was no clear understanding between the interplay among these classification systems. Therefore, the main objective of this work was to make a comparison of concepts of BCS and BDDCS to understand what are the key factors that allow for the integration of these biopharmaceutics classification systems. Also, the suitability of an in situ single-pass intestinal perfusion assay in rats (SPIP) development was assessed by us to determine the limit between high and low permeability following what the FDA BCS guidance suggests. An excellent correlation was found between the values of permeability obtained by applying SPIP assays and the extensions of the metabolism of the set of compounds studied in this work, with the exception of three compounds that showed disparity between their permeability coefficients ( Peff), obtained herein by SPIP, and their metabolism (acetazolamide, azithromycin, and efavirenz). Discrepancies allowed us to elucidate the interrelationship between BCS and BDDCS.

The Effects of Acetazolamide on Exercise Performance at Sea Level and in Hypoxic Environments: A Review.

Lowlanders rapidly ascending to high altitude (>2500 m) often develop acute mountain sickness (AMS). While acclimatization is the most effective method of reducing symptoms of AMS (ie, headache, fatigue, nausea, gastrointestinal distress, etc.), it may take several days to become fully acclimated. Prophylactic use of acetazolamide (AZ), a carbonic anhydrase inhibitor, has become a popular alternative to staged acclimatization because it can be a less time-consuming method of reducing symptoms of AMS. While numerous studies have shown the effectiveness of AZ in mitigating the symptoms of AMS, a review of the existing literature regarding the effects of AZ on submaximal and maximal exercise performance at sea level and at altitude has not been performed. Literature search identified 17 peer reviewed articles examining the effects of AZ on exercise performance both at sea level and at altitude, as well as the associated side effects of prophylactic AZ use for the attenuation of AMS. This review finds that AZ treated cohorts experience a reduction in time to exhaustion during both submaximal and maximal exercise performance at sea level. At altitude, AZ treated cohorts' recorded widely variable submaximal and maximal exercise performance. At sea level, AZ impairs submaximal and maximal exercise performance. Due to the wide variation of findings of previously published studies, the effects of AZ on submaximal and maximal exercise performance at altitude remain unknown.

Objective evaluation of cerebrovascular reactivity for acetazolamide predicts cerebral hyperperfusion after carotid artery stenting: Comparison with region of interest methods.

BACKGROUND AND PURPOSE: Hemodynamic impairments are considered risk factors of cerebral hyperperfusion after carotid artery stenting (CAS); measurement by Single-photon emission computed tomography (SPECT) using a subjective region of interest (ROI) method lacks consistency and reproducibility. MATERIALS AND METHODS: The present study compared objective perfusion analysis (stereotactic extraction estimation [SEE] method) with the ROI method for preoperative SPECT to predict the hyperperfusion phenomenon (HPP) after CAS. Preoperative resting asymmetry index (cerebral blood flow [CBF] ratio from the affected to unaffected hemisphere) and cerebrovascular reactivity (CVR) to acetazolamide were measured by N-isopropyl-p-[123I]-iodoamphetamine SPECT using the SEE and ROI method in 84 patients. CBF was also measured the day after CAS. Perfusion data with the highest area under the curve (AUC) by receiver-operating characteristic (ROC) analysis was considered a perfusion risk factor of HPP. Multivariate analyses for clinical characteristics and perfusion risk factors were performed to determine predictors of HPP. RESULTS: The HPP was observed in 10 patients (11.9%). Female sex, contralateral stenosis, and degree of stenosis were significantly associated with HPP development on univariate analysis, and symptomatic stenosis was not found to be a significant factor. On SPECT analysis, CVR in the MCA area by SEE method had the highest AUC (0.981). Multivariate analysis showed that CVR in the MCA area was a significant predictor of HPP (P=0.041). To predict hyperperfusion, the ROC curve of the CVR showed a cutoff value of -0.60%, sensitivity of 94.6%, and specificity of 100% (P<0.001). CONCLUSIONS: Objective SEE method had better a predictive capability than ROI method to identify risk of hyperperfusion after CAS.

Acetazolamide and Hydrochlorothiazide Followed by Furosemide Versus Furosemide and Hydrochlorothiazide Followed by Furosemide for the Treatment of Adults With Nephrotic Edema: A Randomized Trial.

BACKGROUND: Nephrotic edema is considered refractory if it does not respond to maximum or near-maximum doses of loop diuretics. This condition can be treated with loop diuretics and thiazides. However, animal studies show that the simultaneous downregulation of pendrin with acetazolamide and inhibition of the sodium-chloride cotransporter with hydrochlorothiazide generates significant diuresis, and furosemide administration following a pendrin inhibitor potentiates furosemide's diuretic effect. Therefore, we performed this study to compare the efficacy of acetazolamide and hydrochlorothiazide followed by furosemide versus furosemide and hydrochlorothiazide followed by furosemide for treatment of refractory nephrotic edema. STUDY DESIGN: Randomized, double-blind, 2-arm, parallel trial. SETTING & PARTICIPANTS: 20 patients with refractory nephrotic edema despite treatment with 80mg of furosemide daily and creatinine clearance > 60mL/min. INTERVENTION: Patients were randomly assigned to 2 groups: group 1 (n=10) received 250mg of acetazolamide and 50mg of hydrochlorothiazide daily and group 2 (n=10) received 40mg of furosemide and 50mg of hydrochlorothiazide daily for 1 week in phase 1. In phase 2, both groups received 40mg of furosemide daily for 2 weeks. OUTCOMES: The primary outcome was absolute change in weight before and at the end of each phase. MEASUREMENTS: Weight and 24-hour urine volume at baseline and the end of each phase. RESULTS: The mean weight decrease was of significantly larger magnitude in group 1 compared with group 2 at the end of phase 1 (-1.4±0.52 [SD] vs -0.65±0.41kg; P=0.001) and phase 2 (-1.6±0.84 vs -0.5±0.47kg; P=0.005). The increase in 24-hour urine volume was also significantly higher in group 1 at the end of phase 2. LIMITATIONS: Small sample size, short follow-up duration, and lack of serum bicarbonate and chloride measurement. CONCLUSIONS: Acetazolamide and hydrochlorothiazide followed by furosemide is more effective than furosemide and hydrochlorothiazide followed by furosemide for the treatment of refractory nephrotic edema.

Prophylactic Effect of Oral Acetazolamide against Intraocular Pressure Elevation after Cataract Surgery in Eyes with Glaucoma.

PURPOSE: To confirm the prophylactic effect of oral acetazolamide against increased intraocular pressure (IOP) in the period immediately after cataract surgery in eyes with primary open-angle glaucoma (POAG) and to evaluate the appropriate administration time of oral acetazolamide to prevent IOP elevation. DESIGN: Randomized clinical study. PARTICIPANTS: Ninety eyes of 90 patients with well-controlled POAG scheduled for phacoemulsification. METHODS: Eyes were assigned randomly to 1 of 3 groups: (1) oral acetazolamide (500 mg) administration 1 hour preoperatively, (2) oral acetazolamide (500 mg) administration 3 hours postoperatively, or (3) no acetazolamide administration. Intraocular pressure was measured using a rebound tonometer 1 hour preoperatively, at the conclusion of surgery (adjusted in the range between 15 and 25 mmHg), and 1, 3, 5, 7, and 24 hours postoperatively. The incidence of eyes with IOP elevation more than 100% above the preoperative IOP was compared. MAIN OUTCOME MEASURES: Postoperative IOP and incidence of eyes with marked IOP elevation. RESULTS: Mean IOP 1 hour preoperatively and that at the conclusion of surgery did not differ significantly among groups. In all groups, mean IOP was significantly elevated from 3 to 7 hours postoperatively, and then decreased at 24 hours. At 1 and 3 hours postoperatively, mean IOP was significantly lower in the group receiving oral acetazolamide preoperatively than in the other 2 groups (postoperative administration or no administration; P ≤ 0.0031). At 5, 7, and 24 hours postoperatively, the IOP was significantly lower in both the preoperative and postoperative administration groups than in the nonadministration group (P ≤ 0.0224). Intraocular pressure elevation of more than 100% occurred in 1 eye (3.3%) in the preoperative administration group, 7 eyes (23.3%) in the postoperative administration group, and 8 eyes (26.6%) in the nonadministration group; the incidence was significantly lower in the preoperative administration group (P = 0.0459). CONCLUSIONS: Eyes with POAG experienced short-term IOP elevation from 3 to 7 hours after phacoemulsification. Oral acetazolamide administration 1 hour preoperatively significantly reduced the IOP elevation from 1 to 24 hours, while administration 3 hours postoperatively reduced the IOP elevation at 5 hours or more after surgery.

Effects of early administration of acetazolamide on the duration of mechanical ventilation in patients with chronic obstructive pulmonary disease or obesity-hypoventilation syndrome with metabolic alkalosis. A randomized trial.

BACKGROUND: Metabolic alkalosis (MA) inhibits respiratory drive and may delay weaning from mechanical ventilation (MV). MA is common in CO2-retainer patients that need MV. Acetazolamide (ACTZ) decreases serum bicarbonate concentration and stimulates respiratory drive. This study evaluated the effects of ACTZ on the duration of MV in patients with MA and COPD or obesity hypoventilation syndrome (OHS) intubated with acute respiratory failure. METHODS: Multicenter, randomized, controlled, double-blind study, with COPD or OHS patients with MV < 72 h and initial bicarbonate >28 mmol/L and pH > 7.35. Test-treatment, ACTZ 500 mg or placebo, was daily administered if pH > 7.35 and bicarbonate >26 mmol/L. Clinical, respiratory and laboratory parameters were recorded. RESULTS: 47 patients (36 men) were randomized. There were no significant differences between groups in comorbidities, baseline characteristics or arterial blood gases at inclusion. The mean difference in the duration of MV between placebo and ACTZ group was 1.3 days (95%CI, -2.1-4.8; p = 0.44). Kaplan-Meier curves showed no differences in the duration of MV (Log-Rank p = 0.41). Between-group comparison of estimated marginal means (CI 95%) during MV were, respectively: PaCO2 55 (51-59) vs 48 (47-50) mm Hg, p = 0.002; bicarbonate concentration 34 (32-35) vs 29 (28-30) mmol/L, p < 0.0001; and minute volume 9.7 (8.9-10.4) vs 10.6 (9.2-12.0) L/min, p = 0.26. There were no severe adverse effects with ACTZ administration. CONCLUSIONS: Among patients with MA and COPD or OHS, early treatment with ACTZ did not shorten significantly the duration of MV compared with placebo. TRIAL REGISTRY: clinical.trials.gov; NCT01499485; URL:.www.clinicaltrials.gov.

Cerebral blood flow, transit time, and apparent diffusion coefficient in moyamoya disease before and after acetazolamide.

INTRODUCTION: The goal of this study was to assess the changes in arterial spin labeling (ASL) cerebral blood flow (CBF) and arterial transit time (ATT), and in apparent diffusion coefficient (ADC), before and after an acetazolamide challenge in moyamoya patients, as function of arterial stenosis severity. METHODS: Pre-operative patients diagnosed with moyamoya disease who could undergo MRI at 3.0T were recruited for this study. A multi-delay pseudo-continuous ASL and a diffusion-weighted sequence were acquired before and 15 min after acetazolamide injection. The severity of anterior, middle, and posterior cerebral artery pathology was graded on time-of-flight MR angiographic images. CBF, ATT, and ADC were measured on standardized regions of interest as function of the vessel stenosis severity. RESULTS: Thirty patients were included. Fifty-four percent of all vessels were normal, 28% mildly/moderately stenosed, and 18% severely stenosed/occluded. Post-acetazolamide, a significantly larger CBF (ml/100 g/min) increase was observed in territories of normal (+19.6 ± 14.9) compared to mildly/moderately stenosed (+14.2 ± 27.2, p = 0.007), and severely stenosed/occluded arteries (+9.9 ± 24.2, p < 0.0001). ATT was longer in territories of vessel anomalies compared with normal regions at baseline. ATT decreases were observed in all territories post-acetazolamide. ADC did not decrease after acetazolamide in any regions, and no correlation was found between ADC changes and baseline ATT, change in ATT, or CVR. CONCLUSION: The hemodynamic response in moyamoya disease, as measured with ASL CBF, is impaired mostly in territories with severe arterial stenosis/occlusion, while ATT was prolonged in all non-normal regions. No significant changes in ADC were observed after acetazolamide.

USE OF A CARBONIC ANHYDRASE INHIBITOR IN X-LINKED RETINOSCHISIS: Effect on Cystic-Appearing Macular Lesions and Visual Acuity.

PURPOSE: To evaluate changes in cystic-appearing macular lesions and visual acuity in patients with X-linked retinoschisis while being treated with a carbonic anhydrase inhibitor. METHODS: A retrospective analysis of 68 eyes from 36 patients between the ages of 5 years and 61 years with X-linked retinoschisis were monitored while on a carbonic anhydrase inhibitor. Macular cystic-appearing lesions were monitored with optical coherence tomography. Snellen visual acuity measurements were converted to logarithm of the minimum angle of resolution equivalent Early Treatment Diabetic Retinopathy Study letters for analysis. Analyses for changes in both visual acuity and macular cysts included comparisons between treatment and pretreatment segments. RESULTS: Forty-five eyes (66%) had a reduction of their cysts while on a carbonic anhydrase inhibitor. Twenty eyes (29%) showed no cystic change, whereas 3 eyes (4%) demonstrated worsening of their cysts with treatment when compared with pretreatment. There was a statistically significant improvement in logarithm of the minimum angle of resolution visual acuity while on treatment relative to pretreatment (P < 0.0001). The estimated average Early Treatment Diabetic Retinopathy Study equivalent improvement was 0.09 (slightly less than one line on the Early Treatment Diabetic Retinopathy Study chart) with a 95% confidence interval of 0.08 to 0.11. CONCLUSION: Considering the entire 36 patients in this cohort, while statistically significant, the average improvement in visual acuity was modest. Nonetheless, in individual patients, the improvement was more substantial. Improvement in the extent of cystic macular lesions was observed in a high percentage of cases.

The effect of oral acetazolamide on cystoid macular edema in hydroxychloroquine retinopathy: a case report.

BACKGROUND: Hydroxychloroquine (HCQ) retinopathy can accompany other retinal complications such as cystoid macular edema (CME), which leads to central visual loss. We report a case of CME with HCQ retinopathy that improved with the use of oral acetazolamide, and discussed the possible mechanisms of CME in HCQ retinopathy using multimodal imaging modalities. CASE PRESENTATION: A 62-year-old patient with systemic lupus erythematosus (SLE) and HCQ retinopathy developed bilateral CME with visual decline. Fluorescein angiography (FA) showed fluorescein leakage in the macular and midperipheral area. After treatment with oral acetazolamide (250 mg/day) for one month, CME was completely resolved, best corrected visual acuity (BCVA) improved from 20/50 to 20/25, and FA examination showed decreased dye leakage in the macular and midperipheral areas. CONCLUSIONS: In cases of vision loss in HCQ retinopathy, it is important to consider not only progression of maculopathy, but also development of CME, which can be effectively treated with oral acetazolamide.

Cerebrovascular reactivity in the caudate nucleus, lentiform nucleus and thalamus in patients with carotid artery disease.

BACKGROUND AND PURPOSE: To assess the effect of unilateral large vessel disease upon the cerebral hemodynamic autoregulatory status in the basal ganglia of patients with steno-occlusive internal carotid artery (ICA) disease. MATERIALS AND METHODS: Twenty-five healthy volunteers and 38 patients with a unilateral symptomatic steno-occlusive ICA lesion and were investigated; 20 with a stenosis >50% and 18 with an occlusion. Cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) were assessed with pseudo-continuous arterial spin labeling (ASL) magnetic resonance (MR) imaging before and after administration of acetazolamide. RESULTS: When compared to controls, the CVR in patients with ICA stenosis was significantly lower in the middle cerebral artery (MCA) territory (P<0.05), and in the caudate (P<0.05) and lentiform nucleus (P<0.05) of the hemisphere ipsilateral to the stenosis. The CVR in the caudate nucleus contralateral to the stenosis was significantly lower (P<0.05) as well. In patients with ICA occlusion, the CVR in the hemisphere ipsilateral to the occlusion as well as in the contralateral hemisphere was significantly lower in the MCA territory (P<0.05), the caudate (P<0.05) and lentiform nucleus (P<0.05), and in the thalamus (P<0.05). CONCLUSION: Perfusion ASL MR imaging shows impaired cerebral hemodynamic autoregulation of the basal ganglia in patients with steno-occlusive ICA disease both in the hemisphere ipsilateral as well as in the hemisphere contralateral to the stenosis or occlusion.

Formulation design of oral pediatric Acetazolamide suspension: dose uniformity and physico-chemical stability study.

CONTEXT: The formulation of an active pharmaceutical ingredient (API) as oral solution or suspension in pediatrics is a habitual practice, due to the non-existence of many commercialized medicines in pediatric doses. It is also the simplest way to prepare and administer them to this vulnerable population. The design of a formulation that assures the dose and the system stability depends on the physico-chemical properties of the API. OBJECTIVE: In this study, we formulate a class IV API, Acetazolamide (AZM) as suspension for oral administration to pediatric population. The suspension must comply attributes of quality, safety and efficacy for this route of administration. MATERIALS AND METHODS: We use simple compounding procedures, as well as fewer pure excipients, as recommended for children. Mass and uniformity content assays and physical and chemical stability studies were performed. To quantify the API an UPLC method was used. RESULTS AND DISCUSSION: We verified the physico-chemical stability of the suspensions and that they passed the mass test of the European Pharmacopeia (EP), but not the dose uniformity test. CONCLUSIONS: This reveals that AZM must be formulated as liquid forms with a more complex system of excipients (not usually indicated in pediatrics), or otherwise solid forms capable of assuring uniformity of mass and dose for every dosage unit.

Morphometric evaluation of the delayed cerebral arteries response to acetazolamide test in patients with chronic carotid artery stenosis using computed tomography angiography.

BACKGROUND: The evidence accumulates that the response to acetazolamide test is delayed on the ipsilateral side to stenosis. However, the effect of acetazolamide beyond 30 min after acetazolamide administration remains unknown. The aim of this study was to assess the diameters of anterior cerebral arteries (ACAs), middle cerebral arteries (MCAs) and posterior cerebral arteries (PCAs) before and 60 min after the acetazolamide test. MATERIALS AND METHODS: Seventeen patients with carotid artery stenosis ≥ 90% on the ipsilateral side and ≤ 50% on the contralateral side were enrolled into the study. Diagnosis was based on ultrasonography examination and was confirmed using digital subtractive angiography. In all patients, two computed tomography angiography examinations were carried out; the first was performed before the acetazolamide administration, while the second one was carried out 60 min after injections. RESULTS: In response to the acetazolamide test: PCA diameter diminished in both ipsi- and contra-lateral side to stenosis (from 1.31 to 1.24 mm and from 1.23 to 1.15 mm, respectively), ACA and MCA decreased in the contralateral side to the stenosis (from 1.33 to 1.26 mm and from 2.75 to 2.66 mm, respectively), ACA and MCA increased in the ipsilateral side to the stenosis (from 1.29 to 1.46 mm and from 2.77 to 2.96 mm, respectively). All changes were statistically significant. CONCLUSIONS: There were significant differences in reactivity to acetazolamide challenge between the internal carotid artery (ICA) and vertebrobasilar circulation in patients suffering from chronic carotid artery stenosis. Within the ICA territory, ACA and MCA responses vary in the affected and not affected side.