Carolina Pelegrini Barbosa Gracitelli

Intrinsically Photosensitive Retinal Ganglion Cell Activity Is Associated with Decreased Sleep Quality in Patients with Glaucoma

PURPOSE To use the pupillary light reflex and polysomnography to evaluate the function of intrinsically photosensitive retinal ganglion cells (ipRGCs) and to correlate this function with structural damage in glaucoma. DESIGN Cross-sectional study. PARTICIPANTS A study was conducted on both eyes of 45 participants (32 patients with glaucoma and 13 healthy subjects). METHODS For the pupillary reflex evaluation, patients were tested in the dark using a Ganzfeld system (RETIport; Roland Consult, Brandenburg, Germany); pupil diameter was measured with an eye tracker system. To preferentially stimulate ipRGCs, we used a 1-second 470-nm flash with a luminance of 250 cd/m(2). To stimulate different retinal photoreceptors, we used a 1-second 640-nm flash with a luminance of 250 cd/m(2). All of the subjects underwent polysomnography. Subjects underwent standard automated perimetry and optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec Inc, Dublin, CA). MAIN OUTCOME MEASURES Correlations between ipRGC activity, as measured by the pupillary light reflex, and polysomnography parameters, and correlations between retinal nerve fiber layer (RNFL) thickness and the pupillary light reflex and polysomnography parameters. RESULTS The mean patient ages in the healthy and glaucoma groups were 56.8±7.8 years and 61.5±11.6 years, respectively (P = 0.174). Patients with glaucoma had significantly lower average total sleep time, sleep efficiency, and minimum oxyhemoglobin saturation compared with the healthy subjects (P  = 0.008, P = 0.002, and P = 0.028, respectively). Patients with glaucoma had significantly higher arousal durations after falling asleep and more periodic limb movements (P = 0.002 and P = 0.045, respectively). There was an inverse correlation between the rapid eye movement latency and the peak of the pupillary response to the blue flash (P = 0.004). The total arousals were inversely correlated with the sustained blue flash response (P = 0.029). The RNFL thickness was associated with the peak and sustained responses to the blue flash (P  <  0.001 for both comparisons); however, RNFL thickness was only associated with the mean oxygen desaturation index among the polysomnography parameters (P = 0.023). CONCLUSIONS This study demonstrated that decreased ipRGC function caused by glaucoma affected pupillary response and sleep quality.

A positive association between intrinsically photosensitive retinal ganglion cells and retinal nerve fiber layer thinning in glaucoma.

PURPOSE To assess the integrity of intrinsically photosensitive retinal ganglion cells (ipRGCs) using the pupillary light reflex in glaucoma patients. METHODS A cross-sectional study was conducted, including 76 eyes from 38 patients with primary open-angle glaucoma and 36 eyes from 18 control subjects. The patients were tested in the dark with light stimuli using the Ganzfeld system, and the pupil diameter was measured with the assistance of an eye tracker consisting of two infrared cameras fit to an eyeglass frame. To preferentially stimulate ipRGCs, we used a 1-second 470-nm flash with a luminance of 250 cd/m(2). To stimulate different retinal photoreceptors (cones and rods), we used a 1-second 630-nm flash with a luminance of 250 cd/m(2). Standard automated perimetry (SAP), matrix frequency-doubling technology (FDT), and high-definition optical coherence tomography (Cirrus HD-OCT) were also performed. The correlation between the ipRGC-mediated sustained response following the pupillary light reflex and the structural and functional changes in glaucoma patients was analyzed using generalized estimating equation. RESULTS An association was observed between the average retinal nerve fiber layer (RNFL) thickness, as measured by Cirrus HD-OCT, and the sustained pupillary response to the blue flash (P = 0.024). The severity of glaucoma, based on the mean deviation of SAP (Hodapp-Anderson-Parrish system), was also associated with the sustained response to the blue flash (P = 0.006). CONCLUSIONS This study showed a correlation between the mean RNFL thickness and the pupillary light response. A decrease in the number of ipRGCs is potentially related to the reduced RNFL thickness.

Association between Glucose Levels and Intraocular Pressure: Pre- and Postprandial Analysis in Diabetic and Nondiabetic Patients

The aim of this study was to evaluate the relationship between glucose levels and intraocular pressure (IOP) fluctuation in diabetic and nondiabetic patients. Seventeen nondiabetic and 20 diabetic subjects underwent a complete ophthalmic examination, capillary glucose testing, and applanation tonometry in two distinct situations: first, fasting for at least 8 hours and, second, postprandial measurements. Baseline glucose levels were higher in diabetic patients (P < 0.001). Postprandial IOP was significantly higher than baseline IOP in diabetic (P < 0.001) and nondiabetic patients (P = 0.006). Postprandial glucose levels were significantly higher than baseline measurements in both diabetic (P = 0.005) and nondiabetic patients (P = 0.015). There was a significant association between glucose levels variation and IOP change in both diabetic patients (R 2 = 0.540; P < 0.001) and nondiabetic individuals (R 2 = 0.291; P = 0.025). There is also a significant association between the baseline glucose levels and IOP change in diabetic group (R 2 = 0.445; P = 0.001). In a multivariable model, the magnitude of glucose level change remained significantly associated with IOP variation even including age, baseline IOP, ancestry, and gender as a confounding factor (P < 0.001). We concluded that there is a significant association between blood glucose levels and IOP variation, especially in diabetic patients.

Can glaucoma affect sleep quality

Glaucoma is an optic neuropathy characterized by the progressive loss of retinal ganglion cells (RGCs) and associated morphological changes to the optic nerve and retinal nerve fiber layer (RNFL). Although most RGCs are related with cortical image processing, a small proportion of RGCs, called intrinsically photosensitive RGCs (ipRGCs), are not involved in the thalamo-cortical pathway of image processing and mediate non-image-forming visual functions such as circadian photoentrainment and pupillary light reflex (PLR). In 2000, ipRGCs were described in mammalian inner retina as a new photoreceptor that expresses the photopigment melanopsin. These cells account for approximately 3% of the entire RGC population in the human retina. The ipRGC is most sensitive to short wavelength, i.e., blue light, and directly contributes to the post-illumination pupil response of sustained constriction (>6 s) after the offset of high luminance (250 cd/m). The loss of the ganglion cell population that happens in glaucomatous disease potentially leads to damaged function and/or a decreased number of ipRGCs. The pupillary light reflex test is used as an indicator of the afferent input from the retina and optic nerve. Recently, studies using pupillography with different stimuli tested conditions to target specific retinal ganglion cell subtypes, such as ipRGCs. Evaluating this specific class of RGCs, our group demonstrated a significant correlation between structural damage, as measured based on RNFL thickness, and the sustained response to blue flashes with high luminance during the pupillary light reflex in glaucomatous patients. In addition, we found a significant correlation between the severity of glaucoma, as measured by functional damage and the sustained pu pillary response. The main clinical finding in this study was the correlation between the RNFL thickness and pupillary response. Probably, in the future, with further investigations clinical examination of the pupillary respon se could be used for monitoring glaucoma progression and assessing prognosis. The true impact of ipRGC damage caused by glaucoma on sleep quality or circadian rhythm has only recently been elucidated. In the human brain, the primary circadian pacemaker is the suprachiasmatic nucleus (SCN), and light plays an important role in synchronizing the circadian system. The light intensity seems to influence melatonin secretion, which in turn modulates sleep and the circadian rhythm. The responses driven by photic input from the eyes are transmitted through the retinohypothalamic tract to the SCN and from there to the upper part of the thoracic spinal cord, the superior cervical ganglia, and the pineal gland. The SCN receives photic input from ipRGCs. Their input synchronizes the SCN to the solar day, which keeps the human circadian rhythm close to a 24-hour cycle by driving the nocturnal synthesis of the pineal hormone melatonin and inducing the circadian phase and sleep. Using polysomnography, we showed that compared with healthy subjects, glaucoma patients had worse sleep quality, and the polysomnographic parameters of sleep disorders were associated with a poorer sustained response to the pupillary reflex in glaucoma patients. Therefore, the damage to the ipRGCs caused by glaucoma decreases their input synchronization, thereby leading to sleep disorders. Moreover, some evidence has shown that the damage to ipRGCs caused by glaucoma is also correlated with increased daytime sleepiness as measured by a self-report questionnaire (Epworth sleepiness scale), and this symptom is also correlated with polysomnographic parameters and a decreased sustained pupillary response. It is well known that excessive daytime sleepiness affects the quality of life, daytime function, and mortality. Therefore, these two major non-image-forming functions of ipRGCs should be considered in certain glaucoma evaluations. In fact, certain specific drawbacks of this issue should be mentioned. Until recently, we investigated these non-image-forming visual functions in glaucomatous population using small sample sizes and cross-sectional designs that did not allow the longitudinal association of the pupillometry with the progression of glaucoma. There is a relatively weak association between the RNFL thickness and sustained pupillary response, and the strength of this association varies depending on the severity of the disease. Therefore, the pupillary reflex should be considered a good tool for progression detection but not for glaucoma diagnosis. Using this pupillary test as a surrogate measure for glaucoma instead of existing techniques is thus not recommended. However, a com plete evaluation would also need to include a more thorough assessment of test-retest variability. Although we certainly believe that there is a relationship between glaucoma damage (measured by RNFL thinning) and

Anterior chamber depth during hemodialysis

Background Exacerbation of chronic glaucoma or acute glaucoma is occasionally observed in patients undergoing hemodialysis (HD) because of anterior chamber depth changes during this therapy. Purpose To evaluate anterior chamber depth and axial length in patients during HD sessions. Methods A total of 67 eyes of 35 patients were prospectively enrolled. Axial length and anterior chamber depth were measured using ultrasonic biometry, and these measures were evaluated at three different times during HD sessions. Body weight and blood pressure pre- and post-HD were also measured. Results There was no difference in the axial length between the three measurements (P = 0.241). We observed a significantly decreased anterior chamber depth (P = 0.002) during HD sessions. Conclusion Our results support the idea that there is a change in anterior chamber depth in HD sessions.

Evaluation of magnocellular pathway abnormalities in schizophrenia: a frequency doubling technology study and clinical implications

BACKGROUND Visual processing deficits have been reported for patients with schizophrenia. Previous studies demonstrated differences in early-stage processing of schizophrenics, although the nature, extent, and localization of the disturbance are unknown. The magnocellular and parvocellular visual pathways are associated with transient and sustained channels, but their respective contributions to schizophrenia-related visual deficits remains controversial. PURPOSE The aim of this study was to evaluate magnocellular dysfunction in schizophrenia using frequency doubling technology. METHODS Thirty-one patients with schizophrenia and 34 healthy volunteers were examined. Frequency doubling technology testing was performed in one session, consisting of a 15-minute screening strategy followed by the C-20 program for frequency doubling technology. RESULTS Schizophrenic patients showed lower global mean sensitivity (30,97 ± 2,25 dB) compared with controls (32,17 ± 3,08 dB), p<0.009. Although there was no difference in the delta sensitivity of hemispheres, there was a difference in sensitivity analysis of the fibers crossing the optic chiasm, with lower mean sensitivity in the patient group (28,80 dB) versus controls (30,66 dB). The difference was higher in fibers that do not cross the optic chiasm, with lower mean sensitivity in patients (27,61 dB) versus controls (30,26 dB), p<0.005. CONCLUSIONS Our results suggest that there are differences between global sensitivity and fiber sensitivity measured by frequency doubling technology. The different sensitivity of fibers that do not cross the optic chiasm is consistent with most current etiological hypotheses for schizophrenia. The decreased sensitivity responses in the optic radiations may significantly contribute to research assessing early-stage visual processing deficits for patients with schizophrenia.

Creation of a childhood glaucoma registry database

PURPOSE The aim is creation of a database to register patients diagnosed with childhood glaucoma. Information collection and storage will utilize a digital platform that permits multiple centers to register patients. This registry will be an important tool to evaluate and group patient profiles, thus allowing identification of risk factors, estimating prevalence, and recruiting participants in future studies. METHODS An online form was designed at the Department of Ophthalmology and Visual Sciences of the Federal University of Sao Paulo to create a registry of patients diagnosed with congenital glaucoma. In addition, a pilot study was conducted in the same institution to validate the Google Forms platform that comprises the registry questionnaire. RESULTS Data can be entered online and stored in the cloud. The database allows the acquisition and storage of epidemiological and clinical data, detection of patterns, and evaluation of the current treatment of children with childhood glaucoma. The data from multiple centers can be combined as collection in online and storage is in the cloud. The form is comprehensive and includes social data, gestational history, family history, clinical data on entering the center, and the treatment received. CONCLUSIONS Google Forms is a useful tool for collecting and analyzing statistical data, facilitating the process of registering patients, and analyzing information. Using the online questionnaire, it will be possible to create a multicenter online database that allows identification of risk factors and evaluation of the outcome of interventions and treatment.PURPOSE The aim is creation of a database to register patients diagnosed with childhood glaucoma. Information collection and storage will utilize a digital platform that permits multiple centers to register patients. This registry will be an important tool to evaluate and group patient profiles, thus allowing identification of risk factors, estimating prevalence, and recruiting participants in future studies. METHODS An online form was designed at the Department of Ophthalmology and Visual Sciences of the Federal University of São Paulo to create a registry of patients diagnosed with congenital glaucoma. In addition, a pilot study was conducted in the same institution to validate the Google Forms platform that comprises the registry questionnaire. RESULTS Data can be entered online and stored in the cloud. The database allows the acquisition and storage of epidemiological and clinical data, detection of patterns, and evaluation of the current treatment of children with childhood glaucoma. The data from multiple centers can be combined as collection in online and storage is in the cloud. The form is comprehensive and includes social data, gestational history, family history, clinical data on entering the center, and the treatment received. CONCLUSIONS Google Forms is a useful tool for collecting and analyzing statistical data, facilitating the process of registering patients, and analyzing information. Using the online questionnaire, it will be possible to create a multicenter online database that allows identification of risk factors and evaluation of the outcome of interventions and treatment.

Internal carotid artery aneurysm mimicking normal-tension glaucoma

Differentiating glaucomatous from nonglaucomatous optic disc cupping remains challenging. We present a case of a 48-year-old woman with an internal carotid aneurysm of approximately 3.5 mm × 6.5 mm that mimicked normal-tension glaucoma. The patient had a 2-year history of low vision acuity in her left eye and frontal oppressive headache. Owing to the carotid aneurysm, she developed an asymmetric vertical cup-to-disc ratio above 0.2, and marked inferotemporal neuronal rim loss and pallor of the residual rim were noted in the left disc. She also developed a visual field defect with an arcuate scotoma in the left eye. The patient was referred to a neurosurgeon and underwent endovascular aneurysm occlusion. This case highlights the diagnostic importance of recognizing that many neurological defects remain underdiagnosed.

Assessment of self-esteem and psychological aspects in patients undergoing upper blepharoplasty

Objective: To evaluate the self-esteem and quality-of-life outcomes in patients undergoing upper blepharoplasty. Methods: A cross-sectional study was performed at Federal University of São Paulo. The self-esteem and quality-of-life of 29 patients undergoing upper blepharoplasty were compared with 20 age-matched volunteers from the general population. During preoperative assessment, the patients and volunteers underwent complete ophthalmological examinations and answered two questionnaires: the Rosenberg self-esteem scale (RSES) and the World Health Organization quality of life assessment (WHOQOL-BREF). The RSES is a ten-item questionnaire developed to measure self-esteem that are answered using a four-point scale. The scores range from 0 to 30, and lower scores indicate higher self-esteem. The WHOQOL-BREF is composed of 26 questions divided into four domains. Mean values greater than 5 are considered indicative of very good quality-of-life. Data from the RSES and quality-of-life scores were compared between the two groups using an unpaired ttest. Results: The mean self-esteem scores for the patients and volunteers were 10.31 ± 0.71 and 6.9 ± 0.99, respectively (p < 0.001). The mean response scores for the WHOQOL-BREF questionnaire for the patients and volunteers were 3.67 ± 0.08 and 3.76 ± 0.08, respectively (p = 0.449). For the psychological subscale of the WHOQOL-BREF questionnaire, the results for the patients and volunteers were 3.52 ± 0.09 and 3.78 ± 0.08, respectively (p = 0.041). Conclusions: Subjects who underwent upper blepharoplasty exhibited worse self-esteem based on the RSES. Regarding quality-of-life, as assessed using the WHOQOL-BREF questionnaire, significant differences between the groups were evident in the psychological aspects subscale. Our study confirms the importance of subjecting patients to psychological evaluation prior to upper blepharoplasty.