Charles Bonnet Syndrome Adversely Affects Vision-Related Quality of Life in Patients with Glaucoma.

PURPOSE: To investigate the impact of Charles Bonnet syndrome (CBS) on vision-related quality of life (VRQoL) in patients with glaucoma. DESIGN: Cross-sectional cohort study. PARTICIPANTS: Twenty-four patients with CBS and 42 matched controls without CBS out of 337 patients with open-angle glaucoma (OAG) with visual field (VF) loss. METHODS: A matching technique was used to identify control patients with similar disease stage, best-corrected visual acuity (BCVA) and age to patients with CBS. Patients' VRQoL was determined using the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25). Rasch-calibrated NEI VFQ-25 scores of the CBS group and the control group were compared. Uni- and multivariable regression analysis was used to evaluate the impact of different factors on VRQoL. MAIN OUTCOME MEASURES: Vision-related quality of life in patients with glaucoma with CBS and without CBS. RESULTS: Vision-related quality of life scores were significantly lower in the CBS group than in the control group on both the visual functioning scale with 39 points (95% confidence interval (CI): 30-48) vs. 52 points (95% CI: 46-58) (P = 0.013) and on the socioemotional scale with 45 points (95% CI: 37-53) vs. 58 points (95% CI: 51-65) (P = 0.015). Univariable regression analysis showed that integrated visual field mean deviation (IVF-MD) (r2 = 0.334, P < 0.001), BCVA in the better eye (r2 = 0.117, P = 0.003), and the presence of CBS (r2 = 0.078, P = 0.013) were significantly correlated to VRQoL scores on the visual functioning scale. Integrated visual field mean deviation (r2 = 0.281, P < 0.001), age (r2 = 0.048, P = 0.042), and the presence of CBS (r2 = 0.076, P = 0.015) were significantly correlated to VRQoL scores on the socioemotional scale. Multivariable regression analysis showed that IVF-MD and the presence of CBS accounted for nearly 40% of the VRQoL score on the visual functioning scale (R2 = 0.393, P < 0.001) and for 34% of the VRQoL score on the socioemotional scale (R2 = 0.339, P < 0.001). CONCLUSIONS: Charles Bonnet syndrome had a significant negative association to VRQoL in patients with glaucoma. Presence of CBS should be considered when evaluating VRQoL in patients with glaucoma. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Long-term Impact of Immediate Versus Delayed Treatment of Early Glaucoma: Results From the Early Manifest Glaucoma Trial.

PURPOSE: To compare long-term visual outcomes in the 2 arms of the Early Manifest Glaucoma Trial (EMGT) and determine if delayed treatment was associated with a penalty in terms of visual function. DESIGN: Long-term follow-up of a prospective, randomized controlled clinical trial. METHODS: EMGT was carried out at 2 centers in Sweden; 255 subjects with newly detected, untreated glaucoma were randomized to immediate treatment with topical betaxolol and argon laser trabeculoplasty or to no initial treatment as long as no progression was detected. Subjects were followed prospectively with standard automated perimetry, visual acuity measurements, and tonometry for up to 21 years. Outcomes included vision impairment (VI), the perimetric mean deviation (MD) index and rate of progression, and visual acuity. RESULTS: At study end, percentages of eyes with VI or blindness were slightly higher in the treated group than in the untreated control group, 12.1% vs 11.0%, and 9.4.% vs 6.1% respectively, as were subjects with VI in at least one eye, 19.5% vs 18.7%. The differences were not statistically significant, nor were cumulative incidences of VI in at least one eye. The control group had more field loss than the treatment group, with median MD in the worse eye of -14.73 dB vs -12.85 dB, and rate of progression of -0.74 vs -0.60 dB/y, which was not statistically significant. Differences in visual acuity were minimal. CONCLUSIONS: Delaying treatment did not result in serious penalties. VI occurred at similar proportions in both treatment arms with a slight preponderance in the treatment group, whereas visual field damage was slightly higher in the control group.

Threat to fixation and vision-related quality of life in early open-angle glaucoma - results from the Glaucoma Intensive Treatment Study.

PURPOSE: To determine the effect of glaucomatous visual field (VF) damage close to the point of fixation, called threat-to-fixation (TTF), on vision-related quality of life (VRQoL) in open-angle glaucoma. METHODS: A total of 239 patients from the Glaucoma Intensive Treatment Study (GITS) were included in this analysis. The second VF of patients with newly diagnosed primarily early glaucoma was evaluated for the presence or absence of TTF. TTF was defined as VF loss including one or more of the four innermost test points depressed at p < 1% in the total deviation probability map of Humphrey 24-2 SITA Standard visual fields. VRQoL was evaluated using Rasch-analysed National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) scores. The correlation between VRQoL and TTF was evaluated using uni- and multivariable regression analyses. RESULTS: TTF was present in at least one eye in 115 patients (48%); located in the superior hemifield alone in 47% (54 of 115), in the inferior hemifield alone in 23% (27 of 115), and in 30% (34 of 115) in both hemifields. The median Rasch-calibrated NEI VFQ-25 scores were identical when comparing patients with TTF (VRQoL score 66, 95% CI: 23-100) and those with no-TTF (VRQoL score 66, 95% CI: 21-100) (p = 0.925). Neither the presence of TTF (R2  = -0.004, p = 0.968) nor the location of TTF (R2  = 0.023, p = 0.103) was significantly correlated to Rasch-calibrated NEI VFQ-25 scores. CONCLUSION: The presence of TTF did not influence VRQoL, as measured by the NEI-VFQ-25, in this relatively large group of patients with mainly early glaucoma.

Charles Bonnet Syndrome in Patients with Open-Angle Glaucoma: Prevalence and Correlation to Visual Field Loss.

PURPOSE: To determine the prevalence and characteristics of Charles Bonnet Syndrome (CBS) and its relation to visual field loss (VFL) in patients with open-angle glaucoma (OAG). DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Adult patients (n = 337) with manifest OAG with verified VFL and without significant macular disease or extraocular conditions known to cause visual hallucinations. METHODS: Patients attending the glaucoma outpatient department of the Skåne University hospital, Malmö, Sweden, between April 1, 2018, and December 31, 2018, were consecutively evaluated for inclusion. Potentially eligible patients admitting to having complex visual hallucinations were interviewed to explore the characteristics of their hallucinatory experiences. Recent automated visual field examinations were available for all participants, and swept-source OCT was performed in participants with CBS to rule out previously undiagnosed macular pathology. The correlation between potential risk factors and CBS was evaluated with logistic regression analysis. MAIN OUTCOME MEASURE: Prevalence of CBS in patients with OAG. RESULTS: Charles Bonnet Syndrome was found in 7.1% (95% confidence interval [CI], 4.7-10.6) of patients with OAG. Participants with CBS were more likely to have at least 1 eye with a visual field index (VFI) of ≤30% compared with those without CBS (71% vs. 34.2%; P = 0.001). Although the best-corrected visual acuity (BCVA) in the worse eye was significantly lower in participants with CBS (decimal equivalent of Snellen BCVA: 0.25 vs. 0.6, P = 0.003), 33% of these participants had a BCVA of ≥0.5 in the worse eye. In multivariable analysis, CBS was correlated to the VFI of the better eye (odds ratio, 0.984; 95% CI, 0.969-0.998, P = 0.030) and the BCVA of the worse-seeing eye (odds ratio, 0.210; 95% CI, 0.046-0.952, P = 0.043). CONCLUSIONS: Charles Bonnet Syndrome was not a rare condition in patients with glaucoma. Patients with a combination of advanced VFL and low BCVA had the highest risk of CBS; however, 1 of 3 patients with CBS had a BCVA of ≥0.5 in both eyes. These findings emphasize the importance of being attentive to symptoms of CBS in patients with glaucomatous VFL even when visual acuity is preserved.

Effectiveness of Elevated Intraocular Pressure as a Criterion for Glaucoma Referral After 6 Years of Follow-Up.

PURPOSE: To evaluate the long-term predictive value of the need to treat patients referred by optometric practitioners, regarding glaucoma, in Malmö, Sweden, using intraocular pressure (IOP) as the primary referral criterion. PATIENTS AND METHODS: This retrospective study included 94 of 108 (87%) individuals referred to the Skåne University Hospital in Malmö, Sweden, for elevated IOP during 2012-2013. Data were extracted from patient records by the end of 2019. Positive outcome was defined as glaucoma, treated suspected glaucoma or treated ocular hypertension (OH) at referral or during the follow-up period. Positive predictive values (PPV) were calculated using different hypothetical thresholds for age and IOP-levels. Long-term follow-up was used to evaluate whether the first visit diagnoses would change over time, and if this would affect the effectiveness of the referrals. RESULTS: Elevated IOP was the only referral criterion in 84% (n=79). In 28 patients (35%) among the IOP-only referrals, no ocular disease was found, and 26 patients (33%) had a positive outcome at the first visit. Median follow-up time was 6.4 years. PPV according to diagnosis after follow-up was 42% (95% CI: 32-54%) for IOP-only referrals. Including thresholds of ≥45 years of age in combination with an IOP of ≥25 mmHg in the referral criteria would have reduced the number of IOP-only referrals by 27% (21 of 79), and increased the PPV to 57% (95% CI: 45-71%) at the last visit. No positive outcome would have been missed, among those that were followed-up after the first visit, when applying these thresholds for referral, over a follow-up period of six years. CONCLUSION: Using only elevated IOP as referral criterion showed a poor accuracy for predicting those that require IOP lowering treatment. The long-term follow-up allowed us to verify the applicability of higher hypothetical threshold requirements on age and IOP for glaucoma referrals from optometric practices.

A prospective study on effectiveness of elevated intraocular pressure as a criterion for glaucoma referrals by optometric practitioners in Sweden.

PURPOSE: To evaluate the outcome of referrals for suspected glaucoma based on elevated intraocular pressure (IOP) made by optometric practitioners in Sweden. METHODS: This prospective study included 95 individuals referred to the Skåne University Hospital Malmö, Sweden, during 2019, by optometric practitioners, based on elevated IOP. Positive outcome was defined as a diagnosis of glaucoma, or a diagnosis of suspected glaucoma. Referral accuracy was analysed. Positive predictive values (PPV) of different hypothetical IOP and age thresholds were calculated. RESULTS: In 34% (95% CI: 24-43%) of the referrals, no eye disease was found. Intraocular pressure (IOP) was the only referral criterion in 77% (73/95). The PPV was 35% (95% CI: 25-45%) for all referrals, 27% (95% CI: 16-38%) for IOP-only referrals and 59% (95% CI: 36-82%) for referrals including additional findings. In IOP-only referrals, no definite diagnosis of glaucoma was made in any patients <45 years of age. Applying a theoretical age limit of ≥45 years with a hypothetical IOP limit of ≥25 mmHg in patients 45-69 years and of ≥22 mmHg in patients ≥70 years increased the PPV to 42% (95% CI: 27-57%). IOP-only referrals would have been reduced by 27% without missing any glaucoma cases. CONCLUSION: The overall predictive value of the referrals was poor. Glaucoma resources would have been used more effectively by increasing the required age for IOP-only referrals to ≥45 years in combination with different IOP thresholds for certain age groups.

Three cases of Charles Bonnet Syndrome in patients with advanced glaucomatous visual field loss but preserved visual acuity.

PURPOSE: To describe three cases of Charles Bonnet syndrome (CBS) in glaucoma patients with preserved visual acuity. METHODS: Three glaucoma patients who had taken part in a recent CBS study were interviewed about their hallucinations. The patients underwent macular optical coherence tomography (OCT) of both eyes. The visual function was evaluated with visual field measurement (Humphrey visual field analyser) and visual acuity testing (Snellen scale). RESULTS: All three patients had preserved visual acuity (≥0.5 in both eyes) and at least one eye with advanced visual field defect (Mean Deviation worse than -12.00 decibel). They all reported vivid visual hallucinations with insight into the unreal nature of the hallucinations. CONCLUSION: Charles Bonnet syndrome can occur in glaucoma despite preserved visual acuity. Awareness of this relation is desirable among clinicians, as it will improve communication with patients.

Nestin-expressing vascular wall cells drive development of pulmonary hypertension.

Nestin, a well-known marker of neuronal stem cells, was recently suggested to characterise stem cell-like progenitors in non-neuronal structures during development and tissue repair. Integrating novel morphological approaches (CLARITY), we investigate whether nestin expression defines the proliferating cell population that essentially drives vascular remodelling during development of pulmonary hypertension.The role of nestin was investigated in lungs of nestin-GFP (green fluorescent protein) mice, models of pulmonary hypertension (rat: monocrotaline, SU5416/hypoxia; mouse: hypoxia), samples from pulmonary hypertension patients and human pulmonary vascular smooth muscle cells (VSMCs).Nestin was solely found in lung vasculature and localised to proliferating VSMCs, but not bronchial smooth muscle cells. Nestin was shown to affect cell number and was significantly enhanced in lungs early during development of pulmonary hypertension, correlating well with increased VSMC proliferation, expression of phosphorylated (activated) platelet-derived growth factor receptor ß and downregulation of the smooth muscle cell differentiation marker calponin. At later time points when pulmonary hypertension became clinically evident, nestin expression and proliferation returned to control levels. Increase of nestin-positive VSMCs was also found in human pulmonary hypertension, both in vessel media and neointima.Nestin expression seems to be obligatory for VSMC proliferation, and specifies lung vascular wall cells that drive remodelling and (re-)generation. Our data promise novel diagnostic tools and therapeutic targets for pulmonary hypertension.

Visual impairment and vision-related quality of life in the Early Manifest Glaucoma Trial after 20 years of follow-up.

PURPOSE: To determine the association between vision-related quality of life (VRQOL) and levels of visual function loss in the Early Manifest Glaucoma Trial (EMGT). METHODS: Two hundred and fifty-five patients were included in the EMGT between 1993 and 1997 and followed regularly by ophthalmic examinations. A Swedish translation of the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) was self-administered at several follow-up visits until 2014. We analysed the association between Rasch-calibrated NEI VFQ-25 scores and visual function in the best eye at the final follow-up visit. RESULTS: Ninety-one per cent (233/255) of all participants completed the NEI VFQ-25 at least once. In univariate logistic regression analysis, NEI VFQ-25 scores were modestly associated with visual acuity (VA) (r(2)  = 0.330, p < 0.001), visual field index (VFI) (r(2)  = 0.200, p < 0.001) and perimetric mean deviation (MD) (r(2)  = 0.193, p < 0.001). In multivariate analysis, VA and VFI together accounted for approximately 40% (r(2)  = 0.380) of the NEI VFQ-25 scores. NEI VFQ-25 scores were significantly higher for patients with no visual impairment (mean 73 ± 22) than for visually impaired patients (mean 31 ± 15, p < 0.001). VFI worse than 50% or MD worse than -18 dB was significantly associated with low VRQOL scores (p < 0.001). CONCLUSIONS: Our results support the widespread, albeit arbitrary, use of a better-eye visual field of <50% as an important threshold for a significant reduction in VRQOL.

Threat to fixation at diagnosis and lifetime risk of visual impairment in open-angle glaucoma.

PURPOSE: To investigate whether threat to fixation (TTF) at diagnosis increases the risk of central vision loss and glaucoma blindness. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 309 patients (309 eyes) with glaucoma were followed up until death; 203 patients (65.7%) had primary open-angle glaucoma, and 106 patients (34.2%) had exfoliation glaucoma. METHODS: Study eyes were divided into 2 groups according to TTF in the first glaucomatous visual field: (1) eyes with TTF, defined as visual field loss (VFL) including ≥1 of the 4 innermost points depressed at P < 1% level in 24-2 or 30-2 Humphrey fields; (2) eyes without TTF, defined as VFL only outside the 4 innermost points. Lifetime risk of visual acuity (VA) loss and glaucoma blindness in the 2 groups was compared by logistic regression analysis. A matching technique was used to adjust for differences in disease stage at presentation. The relative influence of TTF on the risk of blindness in the 2 matched groups was analyzed by the Kaplan-Meier method. MAIN OUTCOME MEASURES: Visual acuity <0.3 and blindness from glaucoma (World Health Organization criteria) at last visit. RESULTS: Threat to fixation was detected in 58.9% of the eyes at diagnosis. The frequency of TTF increased with stage of glaucomatous loss: 28.3% in eyes with mean deviation (MD) >-6.00 decibels (dB) versus 95.7% with MD <-20.00 dB. Univariate analysis demonstrated that eyes with TTF at presentation compared with eyes without TTF became blind more often (56/182 [30.8%] vs. 22/127 [17.3%]; P = 0.008) and faster (mean time from diagnosis to blindness, 84.6±50.7 vs. 126.7±51.4 months; P < 0.002). However, in multivariate analysis, TTF was not an independent risk factor for VA <0.3 (odds ratio, 1.43; 95% confidence interval, 0.75-2.74) or blindness (odds ratio, 1.03; 95% confidence interval, 0.52-2.01). With regard to patient survival time, there were no differences between eyes with TTF and eyes without TTF after adjusting for disparities in disease severity at presentation (P = 0.934). CONCLUSIONS: Including TTF in the assessment of risk for glaucoma blindness did not add any important information when the stage of VFL was taken into account.

Histological characterization of mast cell chymase in patients with pulmonary hypertension and chronic obstructive pulmonary disease.

Our previous findings demonstrated an increase in pulmonary mast cells (MCs) in idiopathic pulmonary arterial hypertension (IPAH). Also, literature suggests a potential role for MCs in chronic obstructive pulmonary disease (COPD). However, a comprehensive investigation of lungs from patients is still needed. We systematically investigated the presence/expression of MCs/MC chymase in the lungs of IPAH and COPD patients by (immuno)histochemistry and subsequent quantification. We found that total and perivascular chymase-positive MCs were significantly higher in IPAH patients than in donors. In addition, chymase-positive MCs were located in proximity to regions with prominent expression of big-endothelin-1 in the pulmonary vessels of IPAH patients. Total and perivascular MCs around resistant vessels were augmented and a significant majority of them were degranulated (activated) in COPD patients. While the total chymase-positive MC count tended to increase in COPD patients, the perivascular number was significantly enhanced in all vessel sizes analyzed. Surprisingly, MC and chymase-positive MC numbers positively correlated with better lung function in COPD. Our findings suggest that activated MCs, possibly by releasing chymase, may contribute to pulmonary vascular remodeling in IPAH. Pulmonary MCs/chymase may have compartment-specific (vascular vs. airway) functions in COPD. Future studies should elucidate the mechanisms of MC accumulation and the role of MC chymase in pathologies of these severe lung diseases.

Structural and functional prevention of hypoxia-induced pulmonary hypertension by individualized exercise training in mice.

Pulmonary hypertension (PH) is a disease with a poor prognosis characterized by a vascular remodeling process and an increase in pulmonary vascular resistance. While a variety of reports demonstrated that exercise training exerts beneficial effects on exercise performance and quality of life in PH patients, it is not known how physical exercise affects vascular remodeling processes occurring in hypoxia-induced PH. Therefore, we investigated the effect of individualized exercise training on the development of hypoxia-induced PH in mice. Training effects were compared with pharmacological treatment with the phosphodiesterase 5 inhibitor Sildenafil or a combination of training plus Sildenafil. Trained mice who received Sildenafil showed a significantly improved walking distance (from 88.9 ± 8.1 to 146.4 ± 13.1 m) and maximum oxygen consumption (from 93.3 ± 2.9 to 105.5 ± 2.2% in combination with Sildenafil, to 102.2 ± 3.0% with placebo) compared with sedentary controls. Right ventricular systolic pressure, measured by telemetry, was at the level of healthy normoxic animals, whereas right heart hypertrophy did not benefit from training. Most interestingly, the increase in small pulmonary vessel muscularization was prevented by training. Respective counterregulatory processes were detected for the nitric oxide-soluble guanylate cyclase-phosphodiesterase system. We conclude that individualized daily exercise can prevent vascular remodeling in hypoxia-induced PH.

Factors associated with lifetime risk of open-angle glaucoma blindness.

PURPOSE: To investigate factors associated with bilateral glaucoma blindness, particularly factors available at the time of diagnosis. METHODS: Retrospective chart review of all patients with primary open-angle glaucoma (POAG) or pseudoexfoliative glaucoma (PEXG) followed at the Department of Ophthalmology or Low Vision Center of Skåne University Hospital, Malmö, Sweden, who died between January 2006 and June 2010. Disease stage at diagnosis was defined by a simplified version of Mills' glaucoma staging system using perimetric mean deviation (MD) to define six stages of severity. Blindness was defined according to WHO criteria. We used logistic regression analysis to examine the association between risk factors and glaucoma blindness. RESULTS: Four hundred and 23 patients were included; 60% POAG and 40% PEXG. Sixty-four patients (15%) became blind from glaucoma. Blind patients had significantly longer mean duration with diagnosed disease than patients who did not go blind (14.8 years ± 5.8 versus 10.6 years ± 6.5, p < 0.001). The risk of blindness increased with higher intraocular pressure (IOP) (OR 1.08, 95% CI 1.03-1.13) and with each stage of more advanced field loss at time of diagnosis (OR 1.80 95% CI 1.34-2.41). Older age at death was also associated with an increased risk of blindness (OR 1.09 95% CI 1.03-1.14), while age at diagnosis was unimportant. PEXG was not an independent risk factor for blindness. CONCLUSIONS: Higher IOP and worse visual field status at baseline were important risk factors, as was older age at death.

TGF-ß directs trafficking of the epithelial sodium channel ENaC which has implications for ion and fluid transport in acute lung injury.

TGF-ß is a pathogenic factor in patients with acute respiratory distress syndrome (ARDS), a condition characterized by alveolar edema. A unique TGF-ß pathway is described, which rapidly promoted internalization of the αßγ epithelial sodium channel (ENaC) complex from the alveolar epithelial cell surface, leading to persistence of pulmonary edema. TGF-ß applied to the alveolar airspaces of live rabbits or isolated rabbit lungs blocked sodium transport and caused fluid retention, which--together with patch-clamp and flow cytometry studies--identified ENaC as the target of TGF-ß. TGF-ß rapidly and sequentially activated phospholipase D1, phosphatidylinositol-4-phosphate 5-kinase 1α, and NADPH oxidase 4 (NOX4) to produce reactive oxygen species, driving internalization of ßENaC, the subunit responsible for cell-surface stability of the αßγENaC complex. ENaC internalization was dependent on oxidation of ßENaC Cys(43). Treatment of alveolar epithelial cells with bronchoalveolar lavage fluids from ARDS patients drove ßENaC internalization, which was inhibited by a TGF-ß neutralizing antibody and a Tgfbr1 inhibitor. Pharmacological inhibition of TGF-ß signaling in vivo in mice, and genetic ablation of the nox4 gene in mice, protected against perturbed lung fluid balance in a bleomycin model of lung injury, highlighting a role for both proximal and distal components of this unique ENaC regulatory pathway in lung fluid balance. These data describe a unique TGF-ß-dependent mechanism that regulates ion and fluid transport in the lung, which is not only relevant to the pathological mechanisms of ARDS, but might also represent a physiological means of acutely regulating ENaC activity in the lung and other organs.

Lifetime risk of blindness in open-angle glaucoma.

PURPOSE: To determine the lifetime risk and duration of blindness in patients with manifest open-angle glaucoma (OAG). DESIGN: Retrospective chart review. METHODS: We studied glaucoma patients who died between January 2006 and June 2010. Most glaucoma patients living in the catchment area (city of Malmö; n = 305 000) are managed at the Department of Ophthalmology at Skåne University Hospital in Malmö. From the patient records we extracted visual field status, visual acuity, and low vision or blindness as defined by the World Health Organization (WHO) criteria and caused by glaucoma at the time of diagnosis and during follow-up. We also noted age at diagnosis and death and when low vision or blindness occurred. RESULTS: Five hundred and ninety-two patients were included. At the time of the last visit 250 patients (42.2%) had at least 1 blind eye because of glaucoma, while 97 patients (16.4%) were bilaterally blind, and 12 patients (0.5%) had low vision. Median time with a glaucoma diagnosis was 12 years (<1-29), median age when developing bilateral blindness was 86 years, and median duration of bilateral blindness was 2 years (<1-13). The cumulative incidences of blindness in at least 1 eye and bilateral blindness from glaucoma were 26.5% and 5.5%, respectively, after 10 years, and 38.1% and 13.5% at 20 years. CONCLUSIONS: Approximately 1 out of 6 glaucoma patients was bilaterally blind from glaucoma at the last visit. Median duration of bilateral blindness was 2 years.

Effects of argon laser trabeculoplasty in the Early Manifest Glaucoma Trial.

PURPOSE: To analyze reduction of intraocular pressure (IOP) by argon laser trabeculoplasty (ALT) in the Early Manifest Glaucoma Trial and factors influencing the effect of such treatment. DESIGN: Cohort study based on 127 patients from the treatment group of the Early Manifest Glaucoma Trial, a randomized clinical trial. METHODS: Patients randomized to the treatment arm of the Early Manifest Glaucoma Trial received a standard treatment protocol (topical betaxolol hydrochloride followed by 360-degree ALT) and then were followed up prospectively at 3-month intervals for up to 8 years. One eye per patient was included in the analyses. We investigated the relationship between IOP before ALT and subsequent IOP reduction and other factors that might have influenced the effect of ALT, including stage of the disease, trabecular pigmentation, presence of exfoliation syndrome, and treating surgeon. RESULTS: The mean ± standard deviation IOP before ALT and after betaxolol treatment was 18.1 ± 3.9 mm Hg, and the mean ± standard deviation short-term IOP reduction 3 months after ALT was 2.8 ± 3.9 mm Hg (12.6 ± 20.5%). The IOP before ALT strongly affected IOP reduction (P < .001); each 3-mm Hg higher IOP before ALT value was associated with an additional mean IOP reduction of approximately 2 mm Hg. The treating surgeons also had a significant impact on IOP reduction (P = 0.001), with mean values ranging from 5.8 to -1.3 mm Hg. CONCLUSIONS: In this cohort, which included many patients with low IOP levels, IOP before ALT markedly influenced the IOP reduction induced by ALT, seen as a much larger decrease in eyes with higher IOP before ALT. The treating surgeon also had a significant impact on ALT outcome.

CFTR-dependent Cl- secretion in Xenopus laevis lung epithelium.

In our present study we used preparations from Xenopus laevis lungs to perform electrophysiological Ussing chamber measurements, unidirectional flux measurements, and employed molecular approaches to elucidate the presence and function of a cystic fibrosis transmembrane conductance regulator (CFTR) homolog in this tissue. Application of different CFTR blockers (NPPB (5-nitro-2-(3-phenylpropylamino)benzoic acid), niflumic acid (NFA), glibenclamide, lonidamine, CFTR(inh)-172) to the apical side of the tissues was able to significantly decrease the measured short circuit current (I(SC)) indicating a Cl(-) secretion due to luminal located CFTR channels. This was further supported by a net (36)Cl(-) secretion determined by radioactive tracer flux experiments. Further, Xenopus pulmonary epithelia responded to apical chlorzoxazone exposure - a CFTR activator - and this activated current was inhibited by CFTR(inh)-172. We performed reverse transcription-PCR (RT-PCR) and Western blot analysis and with both approaches we found characteristic signals indicating the presence of a CFTR homolog in Xenopus lung. In addition, we were able to detect CFTR in apical membranes of Xenopus lung slices with immunohistological techniques. We conclude that Xenopus lung epithelium exhibits functional CFTR channels and that this tissue represents a valuable model for the investigation of ion transport properties in pulmonary epithelia.