Evaluation of Verteporfin as a Novel Antifibrotic Agent in a Rabbit Model of Glaucoma Filtration Surgery: A Pilot Study.

Purpose: Verteporfin is a benzoporphyrin derivative which is Food and Drug Administration-approved for treatment of choroidal neovascularization in conjunction with photodynamic therapy. It has been shown to prevent fibrosis and scar formation in several organs and represents a promising novel antifibrotic agent for glaucoma surgery. The goal of this study is to determine the effect of verteporfin on wound healing after glaucoma filtration surgery. Design: Preclinical study using a rabbit model of glaucoma filtration surgery. Subjects: Eight New Zealand white rabbits underwent glaucoma filtration surgery in both eyes. Methods: Eyes were randomized into 4 study groups to receive a postoperative subconjunctival injection of 1 mg/mL verteporfin (n = 4), 0.4 mg/mL mitomycin C (MMC; n = 4), 0.4 mg/mL MMC + 1 mg/mL verteporfin (n = 4), or balanced salt solution (BSS) control (n = 4). Bleb survival, vascularity, and morphology were graded using a standard scale over a 30-day period, and intraocular pressure (IOP) was monitored. At 30 days postoperative or surgical failure, histology was performed to evaluate for inflammation, local toxicity, and scarring. Main Outcome Measures: The primary outcome measure was bleb survival. Secondary outcome measures were IOP, bleb morphology, and bleb histology. Results: Compared to BSS control blebs, verteporfin-treated blebs demonstrated a trend toward increased surgical survival (mean 9.8 vs. 7.3 days, log rank P = 0.08). Mitomycin C-treated blebs survived significantly longer than verteporfin-treated blebs (log rank P = 0.009), with all but 1 MMC-treated bleb still surviving at postoperative day 30. There were no significant differences in survival between blebs treated with combination verteporfin + MMC and MMC alone. Mitomycin C-treated blebs were less vascular than verteporfin-treated blebs (mean vascularity score 0.3 ± 0.5 for MMC vs. 1.0 ± 0.0 for verteporfin, P < 0.01). Bleb histology did not reveal any significant toxicity in verteporfin-treated eyes. There were no significant differences in inflammation or scarring across groups. Conclusions: Although verteporfin remained inferior to MMC with regard to surgical survival, there was a trend toward increased survival compared with BSS control and it had an excellent safety profile. Further studies with variations in verteporfin dosage and/or application frequency are needed to assess whether this may be a useful adjunct to glaucoma surgery. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Differential expression of PIEZO1 and PIEZO2 mechanosensitive channels in ocular tissues implicates diverse functional roles.

PIEZO1 and PIEZO2 are mechanosensitive ion channels that regulate many important physiological processes including vascular blood flow, touch, and proprioception. As the eye is subject to mechanical stress and is highly perfused, these channels may play important roles in ocular function and intraocular pressure regulation. PIEZO channel expression in the eye has not been well defined, in part due to difficulties in validating available antibodies against PIEZO1 and PIEZO2 in ocular tissues. It is also unclear if PIEZO1 and PIEZO2 are differentially expressed. To address these questions, we used single-molecule fluorescence in situ hybridization (smFISH) together with transgenic reporter mice expressing PIEZO fusion proteins under the control of their endogenous promoters to compare the expression and localization of PIEZO1 and PIEZO2 in mouse ocular tissues relevant to glaucoma. We detected both PIEZO1 and PIEZO2 expression in the trabecular meshwork, ciliary body, and in the ganglion cell layer (GCL) of the retina. Piezo1 mRNA was more abundantly expressed than Piezo2 mRNA in these ocular tissues. Piezo1 but not Piezo2 mRNA was detected in the inner nuclear layer and outer nuclear layer of the retina. Our results suggest that PIEZO1 and PIEZO2 are differentially expressed and may have distinct roles as mechanosensors in glaucoma-relevant ocular tissues.

Novel Radiological Brain Anomalies in a Patient with Congenital Muscular Dystrophy due to FKRP Mexican Founder Mutation c.1387A > G: Review of the Literature.

Mutations in the FKRP gene result in phenotypes with severe forms of congenital muscular dystrophies (CMD) and limb-girdle muscular dystrophies. We present a Mexican patient with a pathogenic homozygous mutation in the FKRP gene (c.1387A > G, p.Asn463Asp) and CMD with radiological brain anomalies as disseminated hyperintensity lesions and discrete generalized cortical atrophy. These findings have not been reported to the best of our knowledge in other patients with the same mutation. The mutation c.1387A > G, p.Asn463Asp in the FKRP gene has been described to have a founder effect in central Mexico, since all the patients described to date are of Hispanic origin. Therefore, we emphasize studying mutations in the FKRP gene in Hispanic pediatric patients with clinical suspicion of CMD. Clinical and molecular diagnosis of specific CMD subtypes is needed to help clarify the prognosis, management, and genetic counseling to the patient and families.

Inflammation-relevant microbiome signature of the stroke brain, gut, spleen, and thymus and the impact of exercise.

Stroke remains a significant unmet need in the clinic with few therapeutic options. We, and others, have implicated the role of inflammatory microbiota in stroke secondary cell death. Elucidating this inflammation microbiome as a biomarker may improve stroke diagnosis and treatment. Here, adult Sprague-Dawley rats performed 30 minutes of exercise on a motorized treadmill for 3 consecutive days prior to transient middle cerebral artery occlusion (MCAO). Stroke animals that underwent exercise showed 1) robust behavioral improvements, 2) significantly smaller infarct sizes and increased peri-infarct cell survival and 3) decreasing trends of inflammatory microbiota BAC303, EREC482, and LAB158 coupled with significantly reduced levels of inflammatory markers ionized calcium binding adaptor molecule 1, tumor necrosis factor alpha, and mouse monoclonal MHC Class II RT1B in the brain, gut, spleen, and thymus compared to non-exercised stroke rats. These results suggest that a specific set of inflammatory microbiota exists in central and peripheral organs and can serve as a disease biomarker and a therapeutic target for stroke.

Neurogenesis after Spinal Cord Injury: State of the Art.

Neurogenesis in the adult state is the process of new neuron formation. This relatively infrequent phenomenon comprises four stages: cell proliferation, cell migration, differentiation, and the integration of these cells into an existing circuit. Recent reports suggest that neurogenesis can be found in different regions of the Central Nervous System (CNS), including the spinal cord (SC). This process can be observed in physiological settings; however, it is more evident in pathological conditions. After spinal cord injury (SCI), the activation of microglial cells and certain cytokines have shown to exert different modulatory effects depending on the presence of inflammation and on the specific region of the injury site. In these conditions, microglial cells and cytokines are considered to play an important role in the regulation of neurogenesis after SCI. The purpose of this article is to present an overview on neural progenitor cells and neurogenic and non-neurogenic zones as well as the cellular and molecular regulation of neurogenesis. Additionally, we will briefly describe the recent advances in the knowledge of neurogenesis after SCI.

Progress in progestin-based therapies for neurological disorders.

Hormone therapy, primarily progesterone and progestins, for central nervous system (CNS) disorders represents an emerging field of regenerative medicine. Following a failed clinical trial of progesterone for traumatic brain injury treatment, attention has shifted to the progestin Nestorone for its ability to potently and selectively transactivate progesterone receptors at relatively low doses, resulting in robust neurogenetic, remyelinating, and anti-inflammatory effects. That CNS disorders, including multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), spinal cord injury (SCI), and stroke, develop via demyelinating, cell death, and/or inflammatory pathological pathways advances Nestorone as an auspicious candidate for these disorders. Here, we assess the scientific and clinical progress over decades of research into progesterone, progestins, and Nestorone as neuroprotective agents in MS, ALS, SCI, and stroke. We also offer recommendations for optimizing timing, dosage, and route of the drug regimen, and identifying candidate patient populations, in advancing Nestorone to the clinic.

Immunization with neural-derived peptides increases neurogenesis in rats with chronic spinal cord injury.

AIMS: Immunization with neural-derived peptides (INDP) has demonstrated to be a promising therapy to achieve a regenerative effect in the chronic phase of the spinal cord injury (SCI). Nevertheless, INDP-induced neurogenic effects in the chronic stage of SCI have not been explored. METHODS AND RESULTS: In this study, we analyzed the effect of INDP on both motor and sensitive function recovery; afterward, we assessed neurogenesis and determined the production of cytokines (IL-4, IL-10, and TNF alpha) and neurotrophic factors (BDNF and GAP-43). During the chronic stage of SCI, rats subjected to INDP showed a significant increase in both motor and sensitive recovery when compared to the control group. Moreover, we found a significant increase in neurogenesis, mainly at the central canal and at both the dorsal and ventral horns of INDP-treated animals. Finally, INDP induced significant production of antiinflammatory and regeneration-associated proteins in the chronic stages of SCI. CONCLUSIONS: These findings suggest that INDP has a neurogenic effect that could improve motor and sensitive recovery in the chronic stage of SCI. Moreover, our results also envision the use of INDP as a possible therapeutic strategy for other trauma-related disorders like traumatic brain injury.

Eyeballing stroke: Blood flow alterations in the eye and visual impairments following transient middle cerebral artery occlusion in adult rats.

Middle cerebral artery occlusion in rodents remains a widely used model of ischemic stroke. Recently, we reported the occurrence of retinal ischemia in animals subjected to middle cerebral artery occlusion, owing in part to the circulatory juxtaposition of the ophthalmic artery to the middle cerebral artery. In this study, we examined the eye hemodynamics and visual deficits in middle cerebral artery occlusion-induced stroke rats. The brain and eye were evaluated by laser Doppler at baseline (prior to middle cerebral artery occlusion), during and after middle cerebral artery occlusion. Retinal function-relevant behavioral and histological outcomes were performed at 3 and 14 days post-middle cerebral artery occlusion. Laser Doppler revealed a typical reduction of at least 80% in the ipsilateral frontoparietal cortical area of the brain during middle cerebral artery occlusion compared to baseline, which returned to near-baseline levels during reperfusion. Retinal perfusion defects closely paralleled the timing of cerebral blood flow alterations in the acute stages of middle cerebral artery occlusion in adult rats, characterized by a significant blood flow defect in the ipsilateral eye with at least 90% reduction during middle cerebral artery occlusion compared to baseline, which was restored to near-baseline levels during reperfusion. Moreover, retinal ganglion cell density and optic nerve depth were significantly decreased in the ipsilateral eye. In addition, the stroke rats displayed eye closure. Behavioral performance in a light stimulus-mediated avoidance test was significantly impaired in middle cerebral artery occlusion rats compared to control animals. In view of visual deficits in stroke patients, closely monitoring of brain and retinal perfusion via laser Doppler measurements and examination of visual impairments may facilitate the diagnosis and the treatment of stroke, including retinal ischemia.

A Novel Partial MHC Class II Construct, DRmQ, Inhibits Central and Peripheral Inflammatory Responses to Promote Neuroprotection in Experimental Stroke.

Recognizing that the pathologic progression of stroke is closely associated with aberrant immune responses, in particular the activation of peripheral leukocytes, namely T cells, we hypothesized that finding a treatment designed to inhibit neuroantigen-specific T cells and block cytotoxic monocytes and macrophages may render therapeutic effects in stroke. We previously reported that subcutaneous administration of partial MHC class II constructs promote behavioral and histological effects in stroke mice by centrally promoting a protective M2 macrophage/microglia phenotype in the CNS and peripherally reversing stroke-associated splenic atrophy. Here, we employed a second species using adult Sprague-Dawley rats exposed to the middle cerebral artery occlusion stroke model and observed similar therapeutic effects with a mouse partial MHC class II construct called DRmQ, as evidenced by reductions in stroke-induced motor deficits, infarcts, and peri-infarct cell loss and neuroinflammation. More importantly, we offered further evidence of peripheral sequestration of inflammation at the level of the spleen, which was characterized by attenuation of stroke-induced spleen weight reduction and TNF-ɑ and IL-6 upregulation. Collectively, these results satisfy the Stroke Therapy Academic Industry Roundtable criteria of testing a novel therapeutic in a second species and support the use of partial MHC class II constructs as a stroke therapeutic designed to sequester both central and peripheral inflammation responses in an effort to retard, or even halt, the neuroinflammation that exacerbates the secondary cell death in stroke.

Dependence of dynamic contour and Goldmann applanation tonometries on peripheral corneal thickness.

AIM: To determine the effects of peripheral corneal thickness (PCT) on dynamic contour tonometry(DCT) and Goldmann applanation tonometry (GAT). METHODS: A cross-sectional study. We created a software which calculates the corneal contour (CC) as a function of the radius from the corneal apex to each pixel of the contour. The software generates a central circumference with a radius of 1 mm and the remainder of the cornea is segmented in 5 rings concentric with corneal apex being its diameter not constant around the corneal circumference as a consequence of the irregular CC but keeping constant the diameter of each ring in each direction of the contour. PCT was determined as the mean thickness of the most eccentric ring. Locally weighted scatterplot smoothing (LOWESS) regression was used to determine the pattern of the relationship between PCT and both DCT and GAT respectively. Thereafter, two multivariable linear regression models were constructed. In each of them, the dependant variable was intraocular pressure (IOP) as determined using GAT and DCT respectively. In both of the models the predictive variable was PCT though LOWESS regression pattern was used to model the relationship between the dependant variables and the predictor one. Age and sex were also introduced control variables along with their first-degree interactions with PCT. Main outcome measures include amount of IOP variation explained through regression models (R2) and regression coefficients (B). RESULTS: Subjects included 109 eyes of 109 healthy individuals. LOWESS regression suggested that a 2nd-degree polynomial would be suitable to model the relationship between both DCT and GAT with PCT. Hence PCT was introduced in both models as a linear and quadratic term. Neither age nor sex nor interactions were statistically significant in both models. For GAT model, R2 was 17.14% (F=9.02; P=0.0002), PCT linear term B was -1.163 (95% CI: -1.163, -0.617). PCT quadratic term B was 0.00081 (95% CI: 0.00043, 0.00118). For DCT model R2 was 14.28% (F=9.29; P=0.0002), PCT linear term B was -0.712 (95% CI: -1.052, -0.372), PCT quadratic term was B=0.0005 (95% CI: 0.0003, 0.0007). CONCLUSION: DCT and GAT measurements are conditioned by PCT though this effect, rather than linear, follows a 2nd-degree polynomial pattern.

Correlations between corneal and optic nerve head variables in healthy subjects and patients with primary open angle glaucoma.

AIM: To correlate corneal variables (determined using the Pentacam) with optic nerve head (ONH) variables determined using the Heidelberg retina tomograph (HRT) in healthy subjects and patients diagnosed with primary open angle glaucoma (POAG). METHODS: Measurements were made in 75 healthy eyes and 73 eyes with POAG and correlations examined through Pearson correlation coefficients between the two sets of variables in the two subject groups. The corneal variables determined were corneal volume (CVol), central corneal thickness (CCT), overall corneal thickness (OvCT), the mean thickness of a circular zone centered at the corneal apex of 1 mm radius (zone I) and the mean thickness of several concentric rings, also centered at the apex until the limbus, each of 1 mm width (zones II to VI respectively). The ONH variables were determined using the HRT. RESULTS: The following pairs of variables were correlated in the control group: CCT-disc area (DAr) (-0.48; P<0.0001), Zone I-DAr (-0.503; P<0.0001) and Zone II-DAr (-0.443; P<0.0001); and in the POAG group: CCT-cup-to-disc area ratio (CDRa) (-0.402; P<0.0001), Zone I-CDRa (-0.418; P<0.0001), Zone II-CDRa (-0.405; P=0.006), Zone I-cup shape measure (CSM) (-0.415; P=0.002), Zone II-CSM (-0.405; P=0.001), Zone IV-height variation contour (HVC) (0.378; P=0.002); Zone V-HVC (0.388, P<0.0001). CONCLUSIONS: In the healthy subjects, significant negative correlation was detected between central and paracentral corneal thickness and optic disc area. In contrast, the POAG patients showed significant negative correlation between central and paracentral corneal thickness and the cup-disc ratio and CSM, and positive correlation between peripheral corneal thickness and HVC.

[Charles Bonnet syndrome. A 45-case series]. / Sindrome de Charles Bonnet. Serie de 45 casos.

INTRODUCTION: Charles Bonnet Syndrome (CBS) is a condition characterised by the presence of visual hallucinations, mainly complex, in patients with significant vision loss and without cognitive impairment. The rise in CBS cases is due to an increased life expectancy and to the development of age-related pathologies such as age-related macular degeneration (AMD). PATIENTS AND METHODS: We herein analyse the main characteristics present in 45 patients diagnosed with CBS at the Neuro-ophthalmology Unit in Hospital Clinico San Carlos. The patients were referred from the macular pathology, glaucoma and ocular surface units, as well as from AE, where they were diagnosed with CBS and later confirmed at the Multidisciplinary Unit formed by the ophthalmology, neurology and psychiatry services of the hospital. RESULTS: Women (66.66%) over 80 constituted 68.88% of the patients and mainly had AMD (37.77%). The most prevalent hallucinations described by the patients were of people and faces (35.55%), in colour (66.66%), in movement (80%), had developed over a period of 6 to 12 months (26.66%), had a frequency of 3 episodes per day (35.55%) and lasted between 3 to 5 minutes (35.55%). CONCLUSIONS: CBS is a complex disorder that requires a multidisciplinary approach from neurologists, psychiatrists, general practitioners and ophthalmologists. New studies are needed in order to understand its clinical presentation and behaviour, and thus improve its management.

TITLE: Sindrome de Charles Bonnet. Serie de 45 casos.Introduccion. El sindrome de Charles Bonnet (SCB) es un cuadro clinico que se caracteriza por la presencia de alucinaciones visuales, principalmente complejas, en pacientes con estado cognitivo conservado e importante deterioro de la vision. El incremento del SCB se debe al aumento de la esperanza de vida y al desarrollo de patologias asociadas al envejecimiento, como la degeneracion macular asociada a la edad. Pacientes y metodos. Se estudian las caracteristicas de una serie de 45 pacientes diagnosticados de SCB en la unidad de neurooftalmologia del Hospital Clinico San Carlos. Los pacientes procedian de las unidades de patologia macular, glaucoma, superficie ocular y urgencias, en las que fueron diagnosticados de SCB, que se confirmo en la unidad multidisciplinar formada por oftalmologia, neurologia y psiquiatria del mismo hospital. Resultados. El 66,66% eran mujeres, de mas de 80 anos (68,88%), principalmente con degeneracion macular asociada a la edad (37,77%). Las alucinaciones que los pacientes presentaban con mas frecuencia eran personas y caras (35,55%), en color (66,66%), en movimiento (80%), con un tiempo de evolucion de 6-12 meses (26,66%), frecuencia de tres episodios al dia (35,55%) y de 3-5 minutos de duracion (35,55%). Conclusiones. El SCB es un complejo sindrome cuya incidencia se esta incrementando en nuestras consultas y que precisa un abordaje multidisciplinar entre oftalmologos, neurologos y psiquiatras para evitar diagnosticos erroneos y proporcionar un tratamiento adecuado. Son necesarios nuevos estudios para un conocimiento mas profundo y adecuado del SCB.

Síndrome de Charles Bonnet. Serie de 45 casos / Charles Bonnet syndrome. A 45-case series

Introducción. El síndrome de Charles Bonnet (SCB) es un cuadro clínico que se caracteriza por la presencia de alucinaciones visuales, principalmente complejas, en pacientes con estado cognitivo conservado e importante deterioro de la visión. El incremento del SCB se debe al aumento de la esperanza de vida y al desarrollo de patologías asociadas al envejecimiento, como la degeneración macular asociada a la edad. Pacientes y métodos. Se estudian las características de una serie de 45 pacientes diagnosticados de SCB en la unidad de neurooftalmología del Hospital Clínico San Carlos. Los pacientes procedían de las unidades de patología macular, glaucoma, superficie ocular y urgencias, en las que fueron diagnosticados de SCB, que se confirmó en la unidad multidisciplinar formada por oftalmología, neurología y psiquiatría del mismo hospital. Resultados. El 66,66% eran mujeres, de más de 80 años (68,88%), principalmente con degeneración macular asociada a la edad (37,77%). Las alucinaciones que los pacientes presentaban con más frecuencia eran personas y caras (35,55%), en color (66,66%), en movimiento (80%), con un tiempo de evolución de 6-12 meses (26,66%), frecuencia de tres episodios al día (35,55%) y de 3-5 minutos de duración (35,55%). Conclusiones. El SCB es un complejo síndrome cuya incidencia se está incrementando en nuestras consultas y que precisa un abordaje multidisciplinar entre oftalmólogos, neurólogos y psiquiatras para evitar diagnósticos erróneos y proporcionar un tratamiento adecuado. Son necesarios nuevos estudios para un conocimiento más profundo y adecuado del SCB (AU)

Introduction. Charles Bonnet Syndrome (CBS) is a condition characterised by the presence of visual hallucinations, mainly complex, in patients with significant vision loss and without cognitive impairment. The rise in CBS cases is due to an increased life expectancy and to the development of age-related pathologies such as age-related macular degeneration. Patients and methods. We herein analyse the main characteristics present in 45 patients diagnosed with CBS at the Neuroophthalmology Unit in Hospital Clínico San Carlos. The patients were referred from the macular pathology, glaucoma and ocular surface units, as well as from A&E, where they were diagnosed with CBS and later confirmed at the Multidisciplinary Unit formed by the ophthalmology, neurology and psychiatry services of the hospital. Results. Women (66.66%) over 80 constituted 68.88% of the patients and mainly had age-related macular degeneration (37.77%). The most prevalent hallucinations described by the patients were of people and faces (35.55%), in colour (66.66%), in movement (80%), had developed over a period of 6 to 12 months (26.66%), had a frequency of three episodes per day (35.55%) and lasted between 3 to 5 minutes (35.55%). Conclusions. CBS is a complex disorder that requires a multidisciplinary approach from neurologists, psychiatrists, general practitioners and ophthalmologists. New studies are needed in order to understand its clinical presentation and behaviour, and thus improve its management (AU)

Síndrome de Charles Bonnet desencadenado por brimonidina en paciente con neuropatía óptica hereditaria de Leber / Charles Bonnet’ syndrome triggered by brimonidine in a patient with Leber's hereditary optic neuropathy

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Anatomical characterization of central, apical and minimal corneal thickness.

AIM: To anatomically locate the points of minimum corneal thickness and central corneal thickness (pupil center) in relation to the corneal apex. METHODS: Observational, cross-sectional study, 299 healthy volunteers. Thickness at the corneal apex (AT), minimum corneal thickness (MT) and corneal thickness at the pupil center (PT) were determined using the pentacam. Distances from the corneal apex to MT (MD) and PT (PD) were calculated and their quadrant position (taking the corneal apex as the reference) determined: point of minimum thickness (MC) and point of central thickness (PC) depending on the quadrant position. Two multivariate linear regression models were constructed to examine the influence of age, gender, power of the flattest and steepest corneal axes, position of the flattest axis, corneal volume (determined using the Pentacam) and PT on MD and PD. The effects of these variables on MC and PC were also determined in two multinomial regression models. RESULTS: MT was located at a mean distance of 0.909 mm from the apex (79.4% in the inferior-temporal quadrant). PT was located at a mean distance of 0.156 mm from the apex. The linear regression model for MD indicated it was significantly influenced by corneal volume (B=-0.024; 95%CI: -0.043 to -0.004). No significant relations were identified in the linear regression model for PD or the multinomial logistic regressions for MC and PC. CONCLUSION: MT was typically located at the inferior-temporal quadrant of the cornea and its distance to the corneal apex tended to decrease with the increment of corneal volume.

Síndrome de Charles Bonnet plus / Charles Bonnet plus syndrome

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Prevalence and clinical characteristics of Charles Bonnet syndrome in Madrid, Spain.

PURPOSE: Charles Bonnet syndrome (CBS) is a condition characterized by development of visual hallucinations in patients with no cognitive impairment and significant loss of vision mainly caused by age-related macular degeneration (AMD) or glaucoma. METHODS: This was a study of prevalence and characteristics of CBS diagnosed at the Neuroophthalmic Unit within the Ophthalmology Department of Hospital Clínico San Carlos (HCSC), Madrid, Spain. RESULTS: The CBS prevalence in patients from HCSC Madrid is 0.47%, rising to 15% in patients with low vision. Women over 80 years of age comprised 58.3% of the patients, who mainly had AMD (58.3%). Main characteristics of hallucinations included animals (50%), color (58.3%), moving (75%), 6- to 12-month evolution (50%), three times a day frequency (75%), and 3- to 5-minute duration (50%). CONCLUSIONS: Charles Bonnet syndrome is a complex process that must be treated jointly by ophthalmologists, neurologists, and psychiatrists in order to ensure accurate diagnosis and adequate management. New studies are needed in order to improve awareness of clinical manifestation of this condition, the incidence of which is underestimated due to patients' fear of being branded mentally ill, as well as physicians' lack of knowledge about CBS.

Characterization of the thickness of different corneal zones in glaucoma: effect on dynamic contour, Goldmann and rebound tonometries.

PURPOSE: To characterize five models of corneal thickness circular zoning in a sample of healthy controls and a sample of patients with primary open-angle glaucoma (POAG) and to determine their effect on Goldmann (GAT), dynamic contour (DCT) and rebound tonometers (RT). METHODS: The study participants were 122 controls and 129 cases. Five corneal thickness zoning models (A, B, C, D and E) were constructed. The partitioning pattern consisted of a circle centred at the corneal apex and several concentric rings, until the limbus; the contours of each ring followed the geometry of the corneal contour of each participant. In Model A, the central circle was 1 mm in diameter and five concentric rings were established. Mean was obtained for each zone for both samples and compared between them using a t-test. The effect on the tonometers of central cornel thickness (CCT) and mean thickness of the zones generated was determined through several linear regression models (one per tonometer and per sample). RESULTS: According to a t-test, cases and controls differ in zones I [mean difference (MD): 17.93 µm], V (MD: 25.52 µm) and VI (MD: 31.78 µm) of model A (higher values in the cases sample). RT was affected by CCT (controls: B = 0.089; cases: B = 0.081). DCT was affected by zone IV of model A (controls: B = -0.029; cases: B = -0.012). GAT was affected by CCT (controls: B = 0.043; cases: B = 0.025) and zone III of model A (controls: B = -0.045; cases: B = -0.033). CONCLUSION: Our results highlight the importance of the thickness of other regions of the cornea different from its main centre in discriminating between healthy controls and patients with POAG and in IOP measurements made using DCT, GAT and RT.