A Chronic Ocular-Hypertensive Rat Model induced by Injection of the Sclerosant Agent Polidocanol in the Aqueous Humor Outflow Pathway.

BACKGROUND: To induce a moderate chronic ocular hypertension (OHT) by injecting polidocanol, a foamed sclerosant drug, in the aqueous humor outflow pathway. METHODS: Intraocular pressure (IOP) was monitored for up to 6 months. Pattern and full-field electroretinogram (PERG and ERG) were recorded and retinal ganglion cells (RGC) and retinal nerve fiber layer (RNFL) thickness were assessed in vivo with optical coherence tomography (OCT) and ex vivo using Brn3a immunohistochemistry. RESULTS: In the first 3 weeks post-injection, a significant IOP elevation was observed in the treated eyes (18.47 ± 3.36 mmHg) when compared with the control fellow eyes (12.52 ± 2.84 mmHg) (p < 0.05). At 8 weeks, 65% (11/17) of intervention eyes had developed an IOP increase >25% over the baseline. PERG responses were seen to be significantly reduced in the hypertensive eyes (2.25 ± 0.24 µV) compared to control eyes (1.44 ± 0.19 µV) (p < 0.01) at week 3, whereas the ERG components (photoreceptor a-wave and bipolar cell b-wave) remained unaltered. By week 24, RNFL thinning and cell loss in the ganglion cell layer was first detected (2/13, 15.3%) as assessed by OCT and light microscopy. CONCLUSIONS: This novel OHT rat model, with moderate levels of chronically elevated IOP, and abnormal PERG shows selective functional impairment of RGC.

The S1P1 receptor-selective agonist CYM-5442 protects retinal ganglion cells in endothelin-1 induced retinal ganglion cell loss.

We investigated the feasibility and efficacy of using a specific sphingosine 1-phosphate (S1P1) receptor agonist, CYM-5442, to slow or block retinal ganglion cell (RGC) loss in endothelin-1 (ET-1) induced RGC loss. A single intravitreal injection of ET-1 (20pmol/ul), a potent vasoactive peptide that produces retinal vessels vasoconstriction, was used to induce and characterize RGC-specific cell death. CYM-5442 (1 mgr/kg) or vehicle was administered intraperitoneally for five consecutive days after ET-1-induced RGC loss. The functional extent of RGC loss injury was evaluated with pattern visual evoked potentials (VEP) and electroretinography. RGCs and retinal nerve fiber layer (RNFL) thickness were assessed in vivo using optical coherence tomography and ex vivo using Brn3a immunohistochemistry in flat-mounted retinas. ET-1 caused significant RGC loss and function loss one week after intravitreal injection. VEP showed preserved visual function after CYM-5442 administration compared to vehicle-treated animals (11.95 ± 0.86 µV vs 3.47 ± 1.20 µV, n = 12) (p < 0.05). RNFL was significantly thicker in the CYM treated-animals compared to the vehicle (93.62 ± 3.22 µm vs 77.72 ± 0.35 µm, n = 12) (p < 0.05). Furthermore, Brn3a immunohistochemistry validated this observation, showing significantly higher RGCs numbers in CYM treated rats than in the vehicle group (76,540 ± 303 vs 52,426 ± 1,932 cells/retina, n = 9) (p = 0.05). CYM-5442 administration was associated with significant retinal cleaved caspase-3 deactivation, indicating reduced apoptotic levels. The results of the present study further demonstrate the important role of S1P1 receptor agonists to lessen intravitreal ET-1 induced RGC loss.

The influence of father's child feeding knowledge and practices on children's dietary diversity: a study in urban and rural districts of Northern Ethiopia, 2013.

Infant and young child feeding has been recognised as an essential element to improve growth of children, especially in developing countries where malnutrition among children and its dire consequences are very prevalent. However, little attention has been paid on the influence of fathers on child feeding practices, although fathers are very important in raising well-adjusted, happy and successful children. Therefore, this study aimed to assess the influence of fathers' child feeding knowledge and practice on children's dietary diversity. A community-based comparative cross-sectional study was conducted among 850 eligible urban and rural households with children of 6-23 months. The father and mother of the child were interviewed on children's dietary diversity and fathers' knowledge and practice of child feeding. Nearly half (46%) of the children in the rural district did not meet the minimum dietary diversity, and in the urban district, the rate was even worse (72%). Grains were the common food group given to the children in both districts, whereas flesh food was the least commonly consumed food group. Additionally, low vitamin A-rich food and other fruit and vegetable consumption seem to be a problem in both districts. Almost all dimensions of fathers' knowledge and practice were significantly related to children's minimum dietary diversity; especially, fathers' knowledge of food groups was an important predictor (P-value < 0.001) in both districts. Interventions that focus on the fathers' knowledge of child feeding, especially about food groups, are recommended to improve children's dietary diversity in the study communities.

Health workers' experiences, barriers, preferences and motivating factors in using mHealth forms in Ethiopia.

BACKGROUND: Mobile health (mHealth) applications, such as innovative electronic forms on smartphones, could potentially improve the performance of health care workers and health systems in developing countries. However, contextual evidence on health workers' barriers and motivating factors that may influence large-scale implementation of such interfaces for health care delivery is scarce. METHODS: A pretested semistructured questionnaire was used to assess health workers' experiences, barriers, preferences, and motivating factors in using mobile health forms on smartphones in the context of maternal health care in Ethiopia. Twenty-five health extension workers (HEWs) and midwives, working in 13 primary health care facilities in Tigray region, Ethiopia, participated in this study. RESULTS: Over a 6-month period, a total of 2,893 electronic health records of 1,122 women were submitted to a central computer through the Internet. Sixteen (69.6%) workers believed the forms were good reminders on what to do and what questions needed to be asked. Twelve (52.2%) workers said electronic forms were comprehensive and 9 (39.1%) workers saw electronic forms as learning tools. All workers preferred unrestricted use of the smartphones and believed it helped them adapt to the smartphones and electronic forms for work purposes. With regards to language preference, 18 (78.3%) preferred using the local language (Tigrinya) version of the forms to English. Indentified barriers for not using electronic forms consistently include challenges related to electronic forms (for example, problem with username and password setting as reported by 5 (21.7%), smartphones (for example, smartphone froze or locked up as reported by 9 (39.1%) and health system (for example, frequent movement of health workers as reported by 19 (82.6%)). CONCLUSIONS: Both HEWs and midwives found the electronic forms on smartphones useful for their day-to-day maternal health care services delivery. However, sustainable use and implementation of such work tools at scale would be daunting without providing technical support to health workers, securing mobile network airtime and improving key functions of the larger health system.

Evaluation of visual function and retinal structure in adult amblyopes.

PURPOSE: To evaluate visual function and its relationship to structure in adult amblyopic subjects. METHODS: This observational, cross-sectional study included 24 adult amblyopes and 19 healthy subjects. The amblyopes were separated into three groups: anisometropic amblyopes (n = 15), strabismic amblyopes (n = 5), and strabismic amblyopes with anisometropia (n = 4). The relationships of the multifocal visual evoked potential (VEP) results with the clinical findings and psychophysical (Humphrey visual field) and structural (spectral domain optical coherence tomography) diagnostic test data were then investigated. RESULTS: Significant differences in the multifocal VEP amplitude responses (abnormal cluster defects), combining the interocular and monocular probability analysis, were observed between the anisometropic amblyopic (80%) and nonamblyopic eyes (13.3%) (p < 0.001), whereas in strabismic amblyopia, such defects were found in 100% of the amblyopic and nonamblyopic eyes. Delayed multifocal VEP interocular and monocular latencies were seen in 66.6 and 26.6% of the anisometropic amblyopic and nonamblyopic eyes, with no significant differences between eyes (p = 0.065). Likewise, latency delays were found in 40% of both strabismic amblyopic and nonamblyopic eyes. Multifocal VEP latency showed significant differences between anisometropic and strabismic amblyopic eyes (p = 0.036). Significant agreement was found between the Humphrey visual field and the multifocal VEP visual field defects in the central area of the visual field (p = 0.033). The average retinal nerve fiber layer thickness, foveal and macular thickness, and macular volume, as measured by spectral domain optical coherence tomography, did not show any significant differences between the amblyopic and nonamblyopic eyes and the control group. CONCLUSIONS: Multifocal VEP amplitudes and latencies were significantly affected in amblyopic eyes and, to a lesser extent, in nonamblyopic eyes. Multifocal VEP response latencies were more delayed in anisometropic eyes than in strabismic eyes, suggesting that anisometropic and strabismic amblyopia may represent different neural abnormalities.

Functional assessment of the visual pathway with multifocal visual evoked potentials, and their relationship with disability in patients with multiple sclerosis.

OBJECTIVE: To objectively evaluate the visual function, and the relationship between disability and optic nerve dysfunction, in patients with multiple sclerosis (MS) and optic neuritis (ON), using multifocal visual evoked potentials (mfVEP). METHODS: This observational, cross-sectional study assessed 28 consecutive patients with clinically definite MS, according to the McDonald criteria, and 19 age-matched healthy subjects. Disability was recorded using the Expanded Disability Status Scale (EDSS) score. The patients' mfVEP were compared to their clinical, psychophysical (Humphrey perimetry) and structural (optic coherence tomography (OCT)) diagnostic test data. RESULTS: We observed a significant agreement between mfVEP amplitude and Humphrey perimetry/OCT in MS-ON eyes, and between mfVEP amplitude and OCT in MS but non-ON eyes. We found significant differences in EDSS score between patients with abnormal and normal mfVEP amplitudes. Abnormal mfVEP amplitude defects (from interocular and monocular probability analysis) were found in 67.9% and 73.7% of the MS-ON and MS-non-ON group eyes, respectively. Delayed mfVEP latencies (interocular and monocular probability analysis) were seen in 70.3% and 73.7% of the MS-ON and MS-non-ON groups, respectively. CONCLUSIONS: We found a significant relationship between mfVEP amplitude and disease severity, as measured by EDSS score, that suggested there is a role for mfVEP amplitude as a functional biomarker of axonal loss in MS.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) and glaucomatous optic neuropathy.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is becoming widely accepted as a risk factor for glaucoma. We discuss the proposed mechanism involved in the pathogenesis of glaucoma in OSAHS, and review the published data on the association between these two conditions, as well as papers regarding functional and structural tests related with glaucomatous damage. There is increasing evidence that the prevalence of glaucoma is higher in OSAHS patients, especially in those with severe disease with apnea-hypopnea index (AHI) >30, and also that sleep disorders may be more frequent in patients with glaucoma, especially in those with normal tension glaucoma (NTG). Several ophthalmic signs and symptoms have been associated with this condition. Raised intraocular pressure (IOP), possibly related to increased body mass index, thinning of retinal nerve fiber layer (RNFL), and alteration of visual field (VF) indices has been demonstrated in many studies, in patients with no history of glaucoma or evidence of glaucomatous changes in the ophthalmic examination. A correlation of AHI with RNFL and VF indices has been described in some studies. Finally, corneal thinning, suspicious glaucomatous disc changes and anomalies in electrophysiological tests such as multifocal visual evoked potential have been described in patients with OSAHS, even in patients with normal findings in the optic nerve and VF, suggesting subclinical optic nerve involvement not detectable in conventional ophthalmic examinations. The pathogenesis of optic nerve involvement has been related to vascular and mechanical factors. Vascular factors include recurrent hypoxia with increased vascular resistance, autonomic deregulation, oxidative stress and inflammation linked to hypoxia and subsequent reperfusion, decreased cerebral perfusion pressure and direct hypoxic damage to the optic nerve. Proposed mechanical factors include increased IOP at night related to supine position and obesity, raised intracranial pressure and elastic fiber depletion in the lamina cribosa and/or trabeculum. In conclusion, ophthalmic evaluation should be recommended in patients with severe OSAHS, and the presence of sleep disorders should be investigated in patients with glaucoma, especially in NTG patients and in those with progressive damage despite controlled IOP, as treatment with continuous positive airway pressure may contribute to stabilizing the progression of glaucomatous damage.

Practices and challenges of growth monitoring and promotion in ethiopia: a qualitative study.

The use of growth monitoring and promotion (GMP) has become widespread. It is a potential contributor towards achieving the Millennium Development Goals of halving hunger and reducing child mortality by two-thirds within 2015. Yet, GMP appears to be a prerequisite for good child health but several studies have shown that there is a discrepancy between the purpose and the practice of GMP. The high prevalence of malnutrition in many developing countries seems to confirm this fact. A descriptive qualitative study was carried out from April to September 2011. Focus group discussions and in-depth interviews were conducted amongst mothers and health workers. Data were analyzed using a qualitative content analysis technique, with the support of ATLAS.ti 5.0 software. The results suggest that most mothers were aware of the need for regular weight monitoring while health workers also seemed to be well-aware and to practise GMP according to the international guidelines. However, there was a deficit in maternal knowledge with regard to child-feeding and a lack of basic resources to keep and/or to buy healthful and nutritionally-rich food. Furthermore, the role of the husband was not always supportive of proper child-feeding. In general, GMP is unlikely to succeed if mothers lack awareness of proper child-feeding practices, and if they are not supported by their husbands.

Targeted knockdown of Cerkl, a retinal dystrophy gene, causes mild affectation of the retinal ganglion cell layer.

In order to approach the function of the retinal dystrophy CERKL gene we generated a novel knockout mouse model by cre-mediated targeted deletion of the Cerkl first exon and proximal promoter. The excised genomic region (2.3kb) encompassed the first Cerkl exon, upstream sequences including the proximal promoter and the initial segment of the first intron. The Cerkl-/- mice were viable and fertile. The targeted Cerkl deletion resulted in a knockdown more than a knockout model, given that alternative promoters (unreported at that time) directed basal expression of Cerkl (35%). In situ hybridizations and immunohistochemistry showed that this remnant expression was moderate in the photoreceptors and weak in the ganglion and inner cell layers. Morphological characterization of the Cerkl-/- retinas did not show any gross structural changes, even at 12 months of age. However, some clear and consistent signals of gliosis and retinal stress were detected by the statistically significant increase of i) the glial fibrillary antigen protein (GFAP) expression, and ii) apoptosis, as detected by TUNEL. Remarkably, consistent non-progressive perturbation (from birth up to 12 months of age) of ganglion cells was supported by the decrease of the Brn3a marker expression as well as the reduced oscillatory potentials in the electroretinographic recordings. In conclusion, the Cerkl-/- knockdown shows a mild retinal phenotype, with increased levels of cellular stress and apoptosis indicators, and clear signs of functional alteration at the ganglion cell layer, but no detectable morphological changes.

Evaluation of multifocal visual evoked potentials in patients with Graves' orbitopathy and subclinical optic nerve involvement.

Dysthyroid optic neuropathy is the most serious, although infrequent (8-10 %) complication in Graves' orbitopathy (GO). It is known that early stages of compressive optic neuropathy may produce reversible visual field defects, suggesting axoplasmic stasis rather than ganglion cell death. This observational, cross-sectional, case-control study assessed 34 consecutive patients (65 eyes) with Graves' hyperthyroidism and longstanding GO and 31 age-matched control subjects. The patients' multifocal visual evoked potentials (mfVEP) were compared to their clinical and psychophysical (standard automated perimetry [SAP]) and structural (optic coherence tomography [OCT]) diagnostic test data. Abnormal cluster defects were found in 12.3 % and 3.1 % of eyes on the interocular and monocular amplitude analysis mfVEP probability plots, respectively. As well, mfVEP latencies delays were found in 13.8 and 20 % of eyes on the interocular and monocular analysis probability plots, respectively. Interestingly, 19 % of patients with GO had ocular hypertension, and a strong correlation between intraocular pressure measured at upgaze and mfVEP latency was found. MfVEP amplitudes and visual acuity were significantly related to each other (P < 0.05), but not with the latencies delays. However, relationships between the interocular or monocular mfVEP amplitudes and latencies analysis and SAP indices or OCT data were not statistically significant. One-third of our patients with GO showed changes in the mfVEP, indicating significant subclinical optic nerve dysfunction. In this sense, the mfVEP may be a useful diagnostic tool in the clinic for early diagnosis and monitoring of optic nerve function abnormalities in patients with GO.

Knowledge and performance of the Ethiopian health extension workers on antenatal and delivery care: a cross-sectional study.

BACKGROUND: In recognition of the critical shortage of human resources within health services, community health workers have been trained and deployed to provide primary health care in developing countries. However, very few studies have investigated whether these health workers can provide good quality of care. This study investigated the knowledge and performance of health extension workers (HEWs) on antenatal and delivery care. The study also explored the barriers and facilitators for HEWs in the provision of maternal health care. METHODS: In conducting this research, a cross-sectional study was performed. A total of 50 HEWs working in 39 health posts, covering a population of approximately 195,000 people, were interviewed. Descriptive statistics was used and a composite score of knowledge of HEWs was made and interpreted based on the Ethiopian education scoring system. RESULTS: Almost half of the respondents had at least 5 years of work experience as a HEW. More than half (27 (54%)) of the HEWs had poor knowledge on contents of antenatal care counseling, and the majority (44 (88%)) had poor knowledge on danger symptoms, danger signs, and complications in pregnancy. Health posts, which are the operational units for HEWs, did not have basic infrastructures like water supply, electricity, and waiting rooms for women in labor. On average within 6 months, a HEW assisted in 5.8 births. Only a few births (10%) were assisted at the health posts, the majority (82%) were assisted at home and only 20% of HEWs received professional assistance from a midwife. CONCLUSION: Considering the poor knowledge of HEWs, poorly equipped health posts, and poor referral systems, it is difficult for HEWs to play a key role in improving health facility deliveries, skilled birth attendance, and on-time referral through early identification of danger signs. Hence, there is an urgent need to design appropriate strategies to improve the performance of HEWs by enhancing their knowledge and competencies, while creating appropriate working conditions.

Evaluation of the visual function in obstructive sleep apnea syndrome patients and normal-tension glaucoma by means of the multifocal visual evoked potentials.

BACKGROUND: This study was designed to objectively evaluate visual function and the causal relationship between sleep apnea and optic nerve dysfunction in patients with obstructive sleep apnea syndrome (OSAS) with or without diagnosis of normal-tension glaucoma (NTG) using multifocal visual evoked potentials (mfVEP). METHODS: This observational, cross-sectional study assessed 20 patients with recently diagnosed OSAS with or without NTG. Diagnosis of sleep apnea was based on overnight polysomnography (ApnoeScreen). All participants underwent a complete physical and ophthalmologic examination. MfVEP recordings obtained using VERIS software (Electro-Diagnostic Imaging, San Mateo, USA), SITA-standard 30-2 automated perimetry (Humphrey Visual Field Analyzer II) and optic coherence tomography (Topcon 3D OCT-1000) exams were performed to evaluate the changes. RESULTS: Abnormal mfVEP amplitudes defects (interocular and monocular probability analysis) were found in 40% of the eyes in the non-glaucoma group and in 90% of eyes of the NTG patients. As well, delayed mfVEP latencies (interocular and monocular probability analysis) were seen in 30 and 60% of the eyes of the non-glaucoma and NTG groups, respectively. The average RNFL (retinal nerve fiber layer) thickness was significantly reduced in the NTG eyes compared to the control database and the non-glaucoma eyes. On the Humphrey Visual Field total deviation analysis, all the NTG eyes showed significant clusters of abnormal points but none was detected in the non-glaucoma group eyes. However, the mfVEP amplitude and latency did not show any significant correlation with the standard perimetry and OCT variables, because the mfVEP technique was able to detect far more early visual defects in these patients. Systolic blood pressure, sleep efficiency, arousal index, mean and minimum arterial oxygen saturation (SaO(2)), time SaO(2) < 90%, oxyhemoglobin desaturation index, number of central and mixed apneas and apnea-hipopneas index were shown to be significantly correlated with mfVEP amplitude and latency. CONCLUSIONS: A significant incidence of subclinical optic nerve involvement, not detected with other structural and psychophysics diagnostic techniques was seen by means of the mfVEP. In this sense, the mfVEP may be a useful diagnostic tool in the clinic for early diagnosis and monitoring of optic nerve function abnormalities in patients with OSAS.

The role of health extension workers in improving utilization of maternal health services in rural areas in Ethiopia: a cross sectional study.

BACKGROUND: Community health workers are widely used to provide care for a broad range of health issues. Since 2003 the government of Ethiopia has been deploying specially trained new cadres of community based health workers named health extension workers (HEWs). This initiative has been called the health extension program. Very few studies have investigated the role of these community health workers in improving utilization of maternal health services. METHODS: A cross sectional survey of 725 randomly selected women with under-five children from three districts in Northern Ethiopia. We investigated women's utilization of family planning, antenatal care, birth assistance, postnatal care, HIV testing and use of iodized salt and compared our results to findings of a previous national survey from 2005. In addition, we investigated the association between several variables and utilization of maternal health services using logistic regression analysis. RESULTS: HEWs have contributed substantially to the improvement in women's utilization of family planning, antenatal care and HIV testing. However, their contribution to the improvement in health facility delivery, postnatal check up and use of iodized salt seems insignificant. Women who were literate (OR, 1.85), listened to the radio (OR, 1.45), had income generating activities (OR, 1.43) and had been working towards graduation or graduated as model family (OR, 2.13) were more likely to demonstrate good utilization of maternal health services. A model family is by definition a family which has fulfilled all the packages of the HEP. CONCLUSIONS: The HEWs seem to have substantial contribution in several aspects of utilization of maternal health services but their insignificant contribution in improving health facility delivery and skilled birth attendance remains an important problem. More effort is needed to improve the effectiveness of HEWs in these regards. For example, strengthening HEWs' support for pregnant women for birth planning and preparedness and referral from HEWs to midwives at health centers should be strengthened. In addition, women's participation in income generating activities, access to radio and education could be targets for future interventions.

Multifocal ERG wavelet packet decomposition applied to glaucoma diagnosis.

BACKGROUND: Glaucoma is the second-leading cause of blindness worldwide and early diagnosis is essential to its treatment. Current clinical methods based on multifocal electroretinography (mfERG) essentially involve measurement of amplitudes and latencies and assume standard signal morphology. This paper presents a new method based on wavelet packet analysis of global-flash multifocal electroretinogram signals. METHODS: This study comprised twenty-five patients diagnosed with OAG and twenty-five control subjects. Their mfERG recordings data were used to develop the algorithm method based on wavelet packet analysis. By reconstructing the third wavelet packet contained in the fourth decomposition level (ADAA4) of the mfERG recording, it is possible to obtain a signal from which to extract a marker in the 60-80 ms time interval. RESULTS: The marker found comprises oscillatory potentials with a negative-slope basal line in the case of glaucomatous recordings and a positive-slope basal line in the case of normal signals. Application of the optimal threshold calculated in the validation cases showed that the technique proposed achieved a sensitivity of 0.81 and validation specificity of 0.73. CONCLUSIONS: This new method based on mfERG analysis may be reliable enough to detect functional deficits that are not apparent using current automated perimetry tests. As new stimulation and analysis protocols develop, mfERG has the potential to become a useful tool in early detection of glaucoma-related functional deficits.

Multifocal Visual Evoked Potentials (mfVEP) for the Detection of Visual Field Defects in Glaucoma: Systematic Review and Meta-Analysis.

Some discrepancies have been observed in the diagnostic efficacy of multifocal visual evoked potential (mfVEP) when evaluating visual field defects in glaucoma patients. Therefore, we evaluated the diagnostic precision of the mfVEP in glaucoma to find its best diagnostic indicator. A systematic review and meta-analysis of quantitative studies published up to 1 April 2021 was performed. The methodological quality of the included articles was assessed. Publication bias analysis and heterogeneity tests were performed. The sensitivity, specificity and diagnostic odds ratio were calculated. The area under the curve (AUC) was calculated using the summary of receiver operating characteristics curve. Six studies with a total of 241 patients were included according to the inclusion and exclusion criteria. The AUC was 0.98. There was no evidence of publication bias or threshold effect. The pooled sensitivity and pooled specificity of the mfVEP amplitude for detection of visual field defects in all studies was 0.93 and 0.89, respectively. The positive and negative likelihood ratios of mfVEP amplitude were 6.56 and 0.08, respectively. The amplitude of mfVEP showed a good diagnostic precision in the prediction of visual field defects. Interocular mfVEP amplitude analysis can be a good diagnostic indicator for visual field study.

Evaluation of functional integrity of the retinohypothalamic tract in advanced glaucoma using multifocal electroretinography and light-induced melatonin suppression.

The aim of the study was to investigate the survival of melanopsin-expressing retinal ganglion cells (mRGCs) and the functional integrity of the retinohypothalamic tract in patients with bilateral advanced glaucomatous optic neuropathy by measuring the neuroendocrine light response of the pineal gland. Nine patients with bilateral advanced primary open-angle glaucoma (glaucoma group) and nine normal control subjects (control group) were included in this pilot observational, prospective, case-control study. The best-corrected visual acuity logMAR, standard automated perimetry mean deviation, and the retinal nerve fiber layer thickness determined by optical coherence tomography and multifocal electroretinography were used to evaluate the changes. Melatonin was analyzed in the saliva by radioimmunoassay before and after exposure to bright light (600 lux) for 60 min at night. The advanced glaucoma group did not have any significant nocturnal melatonin suppression after exposure to bright light (14.28 ± 3.07 pg/ml pre-light melatonin concentration vs. 15.22 ± 3.56 pg/ml after light exposure; p = 0.798) unlike the marked melatonin suppression in the control group (22.43 ± 4.37 pg/ml pre-light melatonin concentration vs. 11.25 ± 1.89 pg/ml after light exposure; p < 0.002). Response density estimates by the scalar product amplitude measure for the interval 0-80 ms of the first-order kernel responses were similar in both groups, indicating that outer retinal function was significantly unchanged in the glaucoma group (5.95 ± 0.54 nV/dg^2) compared with the control group (6.20 ± 0.22 nV/dg^2) (p = 0.689). Our findings are consistent with the interpretation that the rhythmic secretion of melatonin was affected in advanced glaucoma, suggesting that attention should be paid to non-image-forming visual functions, such as control of circadian rhythm and the clinical impact in patients with glaucoma.

Short and long term axotomy-induced ERG changes in albino and pigmented rats.

PURPOSE: To investigate the different components of full-field flash electroretinogram (ERG) responses in adult albino and pigmented rats at various time intervals following optic nerve transection (ONT). METHODS: In adult Sprague-Dawley (SD, albino) and Piebald-Viral-Glaxo (PVG, pigmented) rats, the left optic nerve was transected intraorbitally to induce retinal ganglion cell (RGC) death. ERG responses were recorded simultaneously from both eyes beforehand and at 1, 2, 4, and 12 week intervals after ONT. The ERG a- and b-waves and the scotopic threshold responses (STR) were analyzed in scotopic conditions. White light stimuli of intensities ranging from 10(-6) to 10(-4) cd.s.m(-2) were used to record the positive and negative scotopic threshold responses (pSTR and nSTR), while stimulus light intensities ranging from 10(-4) to 10(2) cd.s.m(-2) were used to analyze the a- and b-wave amplitudes of standard ERG recordings. RESULTS: In the albino rats, one week after intraorbital ONT, the STR mean amplitude decreased significantly, to approximately 60% of the values registered for the contralateral eye (p<0.05), which had not been operated on; standard ERG a- and b-waves showed a small reduction in amplitude-to approximately 85%. By two weeks after ONT, the STR mean amplitude was approximately 40% that of the contralateral eye, while the a- and b-wave amplitudes had further decreased to approximately 75%. Four weeks after ONT, the STR had fallen to 60% of that of the contralateral eyes, whereas the a- and b-waves reached values of approximately 90%. Twelve weeks after ONT, the STR remained significantly reduced to approximately 45%, whereas the a- and b-waves reached values of approximately 90%. In the pigmented rats, one week after intraorbital ONT, the mean amplitude had decreased significantly, to approximately 60% for the pSTR and to 80% for the nSTR of the values registered for the intact contralateral eye (p<0.05); while the standard ERG a- and b-waves showed a small reduction in amplitude to approximately 90%. Two weeks after ONT, the STR mean amplitude was approximately 55%, while the a- and b-wave amplitudes had further decreased to approximately 65%. Four weeks after ONT, the STR also was significantly reduced, to only 40%, whereas the a- and b-waves reached values of approximately 60%. Twelve weeks after ONT, the pSTR and nSTR remained significantly reduced to approximately 40% and 70%, respectively; whereas the a- and b-waves reached values of approximately 80%. CONCLUSIONS: Optic nerve injury results in transient reductions of the major ERG components, the a- and b-waves, as well as permanent reductions of the early components of the ERG, the negative and positive scotopic threshold responses. Because ONT induces massive RGC loss, it is likely that permanent reduction in the STR represents a lack of the RGC population, thus highlighting the importance of the STR recordings as an electrophysiological tool for the assessment of RGC function.

Treating amblyopia in adults with prosthetic occluding contact lenses.

PURPOSE: To investigate the feasibility, effectiveness and acceptability of using prosthetic occluding contact lenses (OCLs) to treat moderate amblyopia in adults and of the role of the multifocal visual evoked potential (mfVEP) as a predictor of postamblyopic therapy. METHODS: A comparative, prospective, interventional, case series pilot study with amblyopic adults (mean age: 40 years, range 20-50 years) allocated into two intervention groups: eye patching and OCL. The primary outcome variable was logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), and secondary outcomes were mfVEP amplitude and latency and patients' health-related quality of life National Eye Institute Visual Function Questionnaire (NEI VFQ-25). RESULTS: Significant improvements in pre- to postamblyopic therapy BCVA were seen at 1.5 months in the OCL group [0.29 logMAR, 95% confidence interval (CI): 0.10-0.47 versus 0.11 logMAR, 95% CI: 0.02-0.19; p < 0.001] and eye patching group (0.29 logMAR, 95% CI: 0.17-0.40 versus 0.18 logMAR, 95% CI: 0.12-0.23; p < 0.01). Post-treatment BCVA was inversely related to age (R: 0.009, 95% CI: -0.02 to -0.001; p = 0.04) and the presence of strabismus (R: -0.3, 95% CI: -0.434 to -0.17; p = 0.001). No significant changes in the number and size of the abnormal mfVEP amplitude and latency defects were observed after occlusion. The NEI VFQ-25 composite score showed significant improvement in the OCL users at 12 months compared to eye patching. CONCLUSION: Significant vision improvement can be achieved, making occlusion with OCLs an effective and more acceptable therapy for adults with amblyopia.

Empirical mode decomposition processing to improve multifocal-visual-evoked-potential signal analysis in multiple sclerosis.

OBJECTIVE: To study the performance of multifocal-visual-evoked-potential (mfVEP) signals filtered using empirical mode decomposition (EMD) in discriminating, based on amplitude, between control and multiple sclerosis (MS) patient groups, and to reduce variability in interocular latency in control subjects. METHODS: MfVEP signals were obtained from controls, clinically definitive MS and MS-risk progression patients (radiologically isolated syndrome (RIS) and clinically isolated syndrome (CIS)). The conventional method of processing mfVEPs consists of using a 1-35 Hz bandpass frequency filter (XDFT). The EMD algorithm was used to decompose the XDFT signals into several intrinsic mode functions (IMFs). This signal processing was assessed by computing the amplitudes and latencies of the XDFT and IMF signals (XEMD). The amplitudes from the full visual field and from ring 5 (9.8-15° eccentricity) were studied. The discrimination index was calculated between controls and patients. Interocular latency values were computed from the XDFT and XEMD signals in a control database to study variability. RESULTS: Using the amplitude of the mfVEP signals filtered with EMD (XEMD) obtains higher discrimination index values than the conventional method when control, MS-risk progression (RIS and CIS) and MS subjects are studied. The lowest variability in interocular latency computations from the control patient database was obtained by comparing the XEMD signals with the XDFT signals. Even better results (amplitude discrimination and latency variability) were obtained in ring 5 (9.8-15° eccentricity of the visual field). CONCLUSIONS: Filtering mfVEP signals using the EMD algorithm will result in better identification of subjects at risk of developing MS and better accuracy in latency studies. This could be applied to assess visual cortex activity in MS diagnosis and evolution studies.