Ciliary muscle and anterior segment characteristics in pre-presbyopic adults with Down syndrome.

PURPOSE: Previous research has shown that accommodation deficits are common in individuals with Down syndrome (DS), but the origin and mechanisms behind these deficits are still unknown. The aim of this study was to investigate the characteristics of different ocular structures involved in accommodation, in particular the ciliary muscle (CM), in a population of individuals with DS to further understand this deficit and its mechanisms. METHODS: Thirty-two volunteer participants of pre-presbyopic age with (n = 16) and without DS (n = 16) were recruited. Temporal and nasal images of the CM were acquired using anterior segment optical coherence tomography (AS-OCT) while participants fixated an eccentrically located target. Analysis of CM parameters was undertaken using validated semi-automated software. Axial length, anterior chamber depth, lens thickness and corneal curvature were obtained with the Topcon Aladdin Optical Biometer and Corneal Topographer. Non-cycloplegic refractive error and accommodative ability were obtained with an open-field autorefractor and dynamic retinoscopy, respectively. Independent t-tests were conducted to determine differences in CM and other anterior segment parameters between participants with and without DS. RESULTS: No significant differences were found in the CM parameters studied between participants with and without DS (p > 0.05). In contrast, significant differences were found in visual acuity (p < 0.001), accommodative response (p < 0.001) and corneal curvature (K1 p = 0.003 and K2 p < 0.001) between participants with and without DS. CONCLUSIONS: Despite having poorer accommodation, pre-presbyopic adults with DS do not have a different CM morphology to that found in typically developing adults. These findings suggest that the accommodative deficit found in this population is not due to a mechanical deficit of the CM.

Impact of accommodative insufficiency and accommodative/vergence therapy on ciliary muscle thickness in the eye.

PURPOSE: Recent evidence suggests that the ciliary muscle apical fibres are most responsive to accommodative load; however, the structure of the ciliary muscle in individuals with accommodative insufficiency is unknown. This study examined ciliary muscle structure in individuals with accommodative insufficiency (AI). We also determined the response of the ciliary muscle to accommodative/vergence therapy and increasing accommodative demands to investigate the muscle's responsiveness to workload. METHODS: Subjects with AI were enrolled and matched by age and refractive error with subjects enrolled in another ciliary muscle study as controls. Anterior segment optical coherence tomography was used to measure the ciliary muscle thickness (CMT) at rest (0D), maximum thickness (CMTMAX) and over the area from 0.75 mm (CMT0.75) to 3 mm (CMT3) posterior to the scleral spur of the right eye. For those with AI, the ciliary muscle was also measured at increasing levels of accommodative demand (2D, 4D and 6D), both before and after accommodative/vergence therapy. RESULTS: Sixteen subjects with AI (mean age = 17.4 years, SD = 8.0) were matched with 48 controls (mean age = 17.8 years, SD = 8.2). On average, the controls had 52-72 µm thicker ciliary muscles in the apical region at 0D than those with AI (p = 0.03 for both CMTMAX and CMT 0.75). Differences in thickness between the groups in other regions of the muscle were not statistically significant. After 8 weeks of accommodative/vergence therapy, the CMT increased by an average of 22-42 µm (p ≤ 0.04 for all), while AA increased by 7D (p < 0.001). CONCLUSIONS: This study demonstrated significantly thinner apical ciliary muscle thickness in those with AI and that the ciliary muscle can thicken in response to increased workload. This may explain the mechanism for improvement in signs and symptoms with accommodative/vergence therapy.

Ciliary Muscle Dimension Changes With Accommodation Vary in Myopia and Emmetropia.

Purpose: The purpose of this study was to determine whether accommodation-induced changes in ciliary muscle dimensions vary between emmetropes and myopes, and the effect of the image analysis method. Methods: Seventy adults aged 18 to 27 years consisted of 25 people with emmetropia (spherical equivalent refraction [SER] +0.21 ± 0.36 diopters [D]) and 45 people with myopia (-2.84 ± 1.72 D). There were 23 people with low myopia (>-3 D) and 22 people with moderate myopia (-3 to -6 D). Right eye ciliary muscles were imaged (Visante OCT; Carl Zeiss Meditec) at 0 D and 6 D demands. Measures included ciliary muscle length (CML), ciliary muscle curved length (CMLarc), maximum ciliary muscle thickness (CMTmax), CMT1, CMT2, and CMT3 (fixed distances 1-3 mm from the scleral spur), CM25, CM50, and CM75 (proportional distances 25%-75%). Linear mixed model analysis determined effects of refractive groups, race, and demand on dimensions. Significance was set at P < 0.05. Results: Myopic eyes had greater CML and CMLarc nasally than emmetropic eyes. Myopic eyes had thicker muscles than emmetropic eyes at nasal positions, except CM25 and CMT3, and at CM75 temporally. During accommodation and only nasally, CML reduced in emmetropic and myopic eyes, and CMLarc reduced in myopic eyes only. During accommodation, both nasally and temporally, muscles thickened anteriorly (CMT1 and CM25) and thinned posteriorly (CMT3 and CM75) except for temporal CM75. Moderate myopic eyes had greater temporal CMLarc than low myopic eyes, and the moderate myopes had thicker muscles both nasally and temporally using fixed and proportional distances. Conclusions: People with myopia had longer and thicker ciliary muscles than people with emmetropia. During accommodation, the anterior muscle thickened and the curved nasal muscle length shortened, more in myopic than in emmetropic eyes. The fixed distance method is recommended for repeat measures in the same individual. The proportional distance method is recommended for comparisons between refractive groups.

Intraocular accommodative movements in monkeys; relationship to presbyopia.

Our goal was to quantify the age-related changes in the dynamic accommodative movements of the vitreous and aqueous humor in iridic, aniridic, phakic and aphakic primate eyes. Six bilaterally iridic and four bilaterally iridectomized rhesus monkeys, ranging in age from 6 to 25 years, received a stimulating electrode in the midbrain Edinger-Westphal nucleus to induce accommodation, measured by a Hartinger coincidence refractometer. One of the four iridectomized monkeys underwent unilateral extracapsular and another monkey underwent intracapsular lens extraction. Eyes were imaged utilizing specialized techniques and contrast agents to resolve intraocular structures. During accommodation the anterior hyaloid membrane and the posterior lens capsule bowed backward. Central vitreous fluid and structures/strands moved posteriorly toward the optic nerve region as peripheral vitreous, attached to the vitreous zonule, was pulled forward by ciliary muscle contraction. Triamcinolone particles injected intravitreally were also observed in the anterior chamber and moved from the anterior chamber toward the cleft of the anterior hyaloid membrane and then further posteriorly into the vitreous-filled cleft between the vitreous zonule and the ciliary body pars plana. These accommodative movements occurred in all eyes, and declined with age. There are statistically significant accommodative movements of various intravitreal structures. The posterior/anterior fluid flow between the anterior chamber and the vitreous compartments during accommodation/disaccommodation represents fluid displacement to allow/facilitate lens thickening. The posterior accommodative movement of central vitreous fluid may result from centripetal compression of the anterior tips of the cistern-like structure attached to the vitreous zonule, and posterior displacement of the central trunk of the cistern during ciliary muscle contraction and centripetal muscle movement. The findings may have implications for presbyopia.

The action of ciliary muscle contraction on accommodation of the lens explored with a 3D model.

The eye's accommodative mechanism changes optical power for near vision. In accommodation, ciliary muscle excursion relieves lens tension, allowing it to return to its more convex shape. Lens deformation alters its refractive properties, but the mechanics of ciliary muscle actions are difficult to intuit due to the complex architecture of the tissues involved. The muscle itself comprises three sections of dissimilarly oriented cells. These cells contract, transmitting forces through the zonule fibers and extralenticular structures. This study aims to create a finite element model (FEM) to predict how the action of the ciliary muscle sections leads to lens displacement. The FEM incorporates initialization of the disaccommodated lens state and ciliary muscle contraction, with three muscle sections capable of independent activation, to drive accommodative movement. Model inputs were calibrated to replicate experimentally measured disaccommodated lens and accommodated ciliary muscle shape changes. Additional imaging studies were used to validate model predictions of accommodative lens deformation. Models were analyzed to quantify mechanical actions of ciliary muscle sections in lens deformation and position modulation. Analyses revealed that ciliary muscle sections act synergistically: the circular section contributes most to increasing lens thickness, while longitudinal and radial sections can oppose this action. Conversely, longitudinal and radial sections act to translate the lens anteriorly with opposition from the circular section. This FEM demonstrates the complex interplay of the three sections of ciliary muscle in deforming and translating the lens during accommodation, providing a useful framework for future investigations of accommodative dysfunction that occurs with age in presbyopia.

Morphological analysis of aqueous humor drainage using QD nanoparticles and indocyanine green.

This study represents the first morphological description of the lymphatic drainage of the ciliary body in vivo by comparative hyperspectral fluorescence imaging techniques of Quantum Qdot655 (QD) nanoparticles and indocyanine green (ICG). A volume of 1.25 µl of QD was injected into the left anterior camera of all rats. Similarly,1.25 µl of ICG diluted at a ratio of one-fourth with physiological saline solution was injected into the right anterior camera of all rats. The thickness of the skin in the mandibular area, connective tissue, and the depth of the mandibular lymph node (MLN) made image retrieval difficult. For QD, 302 nm UV excitation and 605 nm fluorescence peak emission were applied. The detection of QD and ICG used in this study in the MLNs is definitive evidence that aqueous humor (AH) follows a uveolymphatic pathway. Scanning electron microscope and the energy dispersive X-ray analyzer spectrum were used to examine both the Schlemm's canal and the MLN. For the first time, the QD was detected in the cortex of MLN. The QCM analysis of both QD-AH and ICG-AH was used to determine whether there was any interaction between them. This comparative study shows the importance of experimental animal modeling in pharmacological studies regarding eye research and drugs. In a female rat, the signal was taken from the parotid lymph node with QD injections.

Emmetropes and myopes differ little in their accommodation dynamics but strongly in their ciliary muscle morphology.

Previous work suggested an association between near vision and myopia. We therefore investigated the accommodation process in emmetropes and myopes regarding morphologic changes of the ciliary muscle (CM) and power changes of the lens for different accommodation demands. The temporal CM of 18 emmetropic and 20 myopic students was imaged via anterior segment optical coherence tomography during far and near accommodation (2.5D, 3D, 4D). Additionally, accommodation dynamics to the stimuli pattern far-near-far (15 s each; 2.5D, 3D, 4D) were recorded with eccentric infrared photorefraction. OCT images were processed using custom-developed software facilitating the analysis of selective CM thickness (CMT) readings and CMT profiles. Anterior CMT readings were significantly smaller in myopes. Starting at 1.4 mm posterior to the scleral spur (SP), myopic CM became thicker than emmetropic. Anterior CMT changes (ΔCMT) continuously increased with accommodation demand in myopes while emmetropic ΔCMT only increased from 2.5D to 3D. Compared to emmetropes, myopes showed smaller ΔCMT but increased CM movement relative to SP. There were no significant differences between the groups for accommodation changes from far to near vision and vice versa, velocity, microfluctuations, power spectra or lag of accommodation. At 4 D, larger ΔCMT were associated with lower lens changes for disaccommodation. While CM shape, movement, and thickness showed distinct differences depending on refractive error, emmetropes and myopes did not differ in their dynamic accommodation. Further analysis is necessary to evaluate whether the CM's anatomical shape or predispositions in its intramuscular constituents are causative factors in myopigenesis.

Multisectorial changes in the ciliary muscle during accommodation measured with high-resolution optical coherence tomography / Alterações multissetoriais no músculo ciliar durante a acomodação com uma tomografía de coerência óptica de alta resolução

ABSTRACT Purpose: To measure changes in the anterior ciliary muscle during accommodation at the nasal, superior, temporal, and inferior sectors by means of an anterior chamber optical coherence tomographer, and correlate them with vergence changes. Methods: Twenty-four subjects with healthy, phakic eyes, whose mean age was 27.1 ± 8.9 years, underwent measurement with an anterior chamber optical coherence tomographer. The anterior ciliary muscle was measured at the nasal, temporal, superior, and inferior sectors for 0, -1, -2, and -3 D of vergence. A linear model was used to assess the correlation of each eye parameter with the accommodative demand. Results: The anterior ciliary muscle area significantly increased with accommodation for each sector, with a maximum increase of about 30% for the nasal-temporal sectors and about 25% for the inferior-temporal sectors. The linear model showed a tendency toward a positive relationship between change in the ciliary muscle area of each sector and vergence. Conclusion: The anterior ciliary muscle area tends to increase with accommodation, although the increase has been shown to be symmetric between the pair sectors superior-nasal and inferior-temporal. These results may help to increase understanding of accommodation biometry and biomechanics.

RESUMO Objetivo: Medir as alterações do músculo ciliar anterior durante a acomodação nos setores nasal, superior, temporal e inferior, através de um tomógrafo de coerência óptica de câmara anterior, e correlacioná-las com alterações de vergência. Métodos: Vinte e quatro indivíduos com olhos saudáveis e fácicos, com idade média de 27,1 ± 8,9 anos, foram submetidos à medida com um tomógrafo de coerência óptica de câmara anterior. O músculo ciliar anterior foi medido nos setores nasal, temporal, superior e inferior para 0, -1, -2 e -3D de vergência. Um modelo linear foi utilizado para avaliar a correlação de cada parâmetro do olho com a demanda acomodativa. Resultados: A área do músculo ciliar anterior aumentou significativamente com a acomodação em cada setor, com um aumento máximo foi de cerca de 30% para os setores naso-temporais, e cerca de 25% para os inferiores-temporais. O modelo linear mostrou uma tendência para uma relação positiva entre a alteração da área do músculo ciliar de cada setor e a vergência. Conclusão: A área do músculo ciliar anterior tende a aumentar com a acomodação, embora o aumento tenha se mostrado simétrico entre os setores superior-nasal e inferior-temporal. Estes resultados podem ajudar a aumentar a compreensão da biometria e biomecânica da acomodação.

Effect of age in the ciliary muscle during accommodation: Sectorial analysis / Efecto de la edad en el músculo ciliar durante la acomodación: análisis sectorial

Purpose: To compare changes in the ciliary muscle area at different sectors between pre-presbyopic and presbyopic eyes during accommodation by means of an anterior segment optical coherence tomographer (OCT). Methods: The anterior ciliary muscle area was measured in 20 healthy and phakic pre-presbyopic eyes, whose mean age was 23.3 ± 4.4 years, and in 20 healthy and phakic presbyopic eyes, whose mean age was 46.5 ± 5.2 years. The relative change in the cross-sectional area of the ciliary muscle was measured at the nasal, inferior, and temporal sectors between 0 and - 3 D of vergence, in -1 D step. A linear model was used to assess the correlation of each eye parameter with the accommodative demand. Results: Each population group showed a significant increase in the anterior ciliary muscle area for each sector. The maximum increase in the ciliary muscle area within the pre-presbyopic group was about 30%, and for the presbyopic one was about 25%. At the same time, it was obtained that the larger the vergence, the larger the variability. Furthermore, the linear model showed a positive tendency between the change in the ciliary muscle area of each sector and the vergence for both population groups, which coefficient of determination was in all cases greater than 0.93. Conclusion: The anterior ciliary muscle area tends to increase with accommodation. The presbyopic nasal, inferior, and temporal ciliary muscle seem to have the same contractile capability as the young presbyopic ciliary muscle. These results might help to increase the evidences in the knowledge regarding the modern understanding of accommodation biometry and biomechanics

Objetivo: Comparar los cambios en el área del músculo ciliar en diferentes sectores entre ojos con pre-presbicia y presbicia durante la acomodación, por medio de un tomógrafo de coherencia óptica (OCT) de segmento anterior. Métodos: Se midió el área del músculo ciliar en 24 ojos sanos fáquicos y con pre-presbicia, con edad media de 23,3 ± 4,4 años, y en 20 ojos sanos fáquicos y con presbicia, con edad media de 46,5 ± 5,2 años. El cambio relativo en el área transeccional del músculo ciliar se midió en los sectores nasal, inferior y temporal entre 0 y -3 D de vergencia, en pasos de -1D. Se utilizó un modelo lineal para valorar la correlación de cada parámetro del ojo con la demanda acomodativa. Resultados: Cada grupo de población reflejó un incremento significativo en el área del músculo ciliar para cada sector. El incremento máximo en el área del músculo ciliar en el grupo de pre-presbicia fue de alrededor del 30%, y para el grupo de presbicia de cerca del 25%. También se observó que cuanto mayor era la vergencia, mayor era la variabilidad. Además, el modelo lineal reflejó una tendencia positiva entre el cambio en el área del músculo ciliar de cada sector y la vergencia para ambos grupos de población, cuyo coeficiente de determinación fue en todos los casos superior a 0,93. Conclusión: El área anterior del músculo ciliar tiende a incrementarse con la acomodación. El músculo ciliar en los sectores nasal, inferior y temporal en la presbicia parece tener la misma capacidad contráctil que el músculo ciliar pre-presbicia. Estos resultados podrían ayudar a incrementar las evidencias en el conocimiento relativo a la comprensión moderna de la biometría de acomodación y la biomecánica

Multisectorial changes in the ciliary muscle during accommodation measured with high-resolution optical coherence tomography.

PURPOSE: To measure changes in the anterior ciliary muscle during accommodation at the nasal, superior, temporal, and inferior sectors by means of an anterior chamber optical coherence tomographer, and correlate them with vergence changes. METHODS: Twenty-four subjects with healthy, phakic eyes, whose mean age was 27.1 ± 8.9 years, underwent measurement with an anterior chamber optical coherence tomographer. The anterior ciliary muscle was measured at the nasal, temporal, superior, and inferior sectors for 0, -1, -2, and -3 D of vergence. A linear model was used to assess the correlation of each eye parameter with the accommodative demand. RESULTS: The anterior ciliary muscle area significantly increased with accommodation for each sector, with a maximum increase of about 30% for the nasal-temporal sectors and about 25% for the inferior-temporal sectors. The linear model showed a tendency toward a positive relationship between change in the ciliary muscle area of each sector and vergence. CONCLUSION: The anterior ciliary muscle area tends to increase with accommodation, although the increase has been shown to be symmetric between the pair sectors superior-nasal and inferior-temporal. These results may help to increase understanding of accommodation biometry and biomechanics.

Effect of age in the ciliary muscle during accommodation: Sectorial analysis.

PURPOSE: To compare changes in the ciliary muscle area at different sectors between pre-presbyopic and presbyopic eyes during accommodation by means of an anterior segment optical coherence tomographer (OCT). METHODS: The anterior ciliary muscle area was measured in 20 healthy and phakic pre-presbyopic eyes, whose mean age was 23.3±4.4 years, and in 20 healthy and phakic presbyopic eyes, whose mean age was 46.5±5.2 years. The relative change in the cross-sectional area of the ciliary muscle was measured at the nasal, inferior, and temporal sectors between 0 and -3 D of vergence, in -1 D step. A linear model was used to assess the correlation of each eye parameter with the accommodative demand. RESULTS: Each population group showed a significant increase in the anterior ciliary muscle area for each sector. The maximum increase in the ciliary muscle area within the pre-presbyopic group was about 30%, and for the presbyopic one was about 25%. At the same time, it was obtained that the larger the vergence, the larger the variability. Furthermore, the linear model showed a positive tendency between the change in the ciliary muscle area of each sector and the vergence for both population groups, which coefficient of determination was in all cases greater than 0.93. CONCLUSION: The anterior ciliary muscle area tends to increase with accommodation. The presbyopic nasal, inferior, and temporal ciliary muscle seem to have the same contractile capability as the young presbyopic ciliary muscle. These results might help to increase the evidences in the knowledge regarding the modern understanding of accommodation biometry and biomechanics.

The peripheral eye: A neurogenic area with potential to treat retinal pathologies?

Numerous degenerative diseases affecting visual function, including glaucoma and retinitis pigmentosa, are produced by the loss of different types of retinal cells. Cell replacement therapy has emerged as a promising strategy for treating these and other retinal diseases. The retinal margin or ciliary body (CB) of mammals has been proposed as a potential source of cells to be used in degenerative conditions affecting the retina because it has been reported it might hold neurogenic potential beyond embryonic development. However, many aspects of the origin and biology of the CB are unknown and more recent experiments have challenged the capacity of CB cells to generate different types of retinal neurons. Here we review the most recent findings about the development of the marginal zone of the retina in different vertebrates and some of the mechanisms underlying the proliferative and neurogenic capacity of this fascinating region of the vertebrates eye. In addition, we performed experiments to isolate CB cells from the mouse retina, generated neurospheres and observed that they can be expanded with a proliferative ratio similar to neural stem cells. When induced to differentiate, cells derived from the CB neurospheres start to express early neural markers but, unlike embryonic stem cells, they are not able to fully differentiate in vitro or generate retinal organoids. Together with previous reports on the neurogenic capacity of CB cells, also reviewed here, our results contribute to the current knowledge about the potentiality of this peripheral region of the eye as a therapeutic source of functional retinal neurons in degenerative diseases.

Presbyopia: Effectiveness of correction strategies.

Presbyopia is a global problem affecting over a billion people worldwide. The prevalence of unmanaged presbyopia is as high as 50% of those over 50 years of age in developing world populations, due to a lack of awareness and accessibility to affordable treatment, and is even as high as 34% in developed countries. Definitions of presbyopia are inconsistent and varied, so we propose a redefinition that states "presbyopia occurs when the physiologically normal age-related reduction in the eye's focusing range reaches a point, when optimally corrected for distance vision, that the clarity of vision at near is insufficient to satisfy an individual's requirements". Strategies for correcting presbyopia include separate optical devices located in front of the visual system (reading glasses) or a change in the direction of gaze to view through optical zones of different optical powers (bifocal, trifocal or progressive addition spectacle lenses), monovision (with contact lenses, intraocular lenses, laser refractive surgery and corneal collagen shrinkage), simultaneous images (with contact lenses, intraocular lenses and corneal inlays), pinhole depth of focus expansion (with intraocular lenses, corneal inlays and pharmaceuticals), crystalline lens softening (with lasers or pharmaceuticals) or restored dynamics (with 'accommodating' intraocular lenses, scleral expansion techniques and ciliary muscle electrostimulation); these strategies may be applied differently to the two eyes to optimise the range of clear focus for an individual's task requirements and minimise adverse visual effects. However, none fully overcome presbyopia in all patients. While the restoration of natural accommodation or an equivalent remains elusive, guidance is given on presbyopic correction evaluation techniques.

Biomechanics of the human lens and accommodative system: Functional relevance to physiological states.

The ability of the human lens to accommodate is mediated by the ciliary muscle and zonule; the manifest optical power changes depend on the shape and material properties of the lens. The latter are difficult to measure with accuracy and, given the dynamic aspects of accommodation and the ageing of cells and tissues, the biomechanics of the lens is neither fixed nor constant. A range of techniques have been developed to measure both ageing trends and spatial variations in the mechanical properties and these have yielded a diverse array of findings and respective conclusions. The majority of quasi-static measurements, where the observation time is in minutes or hours, indicate that the stiffness of the lens increases with age at a faster rate in the lens centre than in the periphery. Dynamic measurements show that lens material properties are dependent on the loading frequency. Recent in vivo analyses suggest that, along the optic axis, profiles of elastic moduli are very similar to profiles of refractive index. This review assesses the advantages and limitations of different measurement techniques and consequent variations in elastic moduli that have been found. Consideration is given to the role of computational modelling and the various modelling methods that have been applied. The changes in mechanical properties of the lens associated with ageing and pathology and future implications for implant design are discussed.

Adrenal and Glucocorticoid Effects on the Circadian Rhythm of Murine Intraocular Pressure.

Purpose: Intraocular pressure (IOP) fluctuates with a robust circadian rhythm, which is synchronized to organismal rhythmicity through the master circadian clock located in the suprachiasmatic nuclei. The mechanisms maintaining circadian synchrony between the suprachiasmatic nuclei and IOP rhythms are presently unknown. The purpose of this study was to evaluate the necessity and sufficiency of adrenal and glucocorticoid function for the entrainment of iris-ciliary body (iris-CB) and IOP circadian rhythms in mice. Methods: Iris-CB complexes were dissected from C57Bl/6J mice that were kept in 12-hour light/dark cycles at 3-hour intervals, and their core clock gene (Per1, Per2, and Bmal1) and glucocorticoid receptor mRNA expression were quantified. Iris-CB complexes from period2::luciferase mice were dissected and cultured to measure in vitro rhythmicity. To determine the phase-shifting effect of glucocorticoids on the iris-CB, dexamethasone or vehicle was added to the cultured tissues at defined circadian phases. The diurnal IOP rhythms of adrenalectomized or sham-operated mice under the 12-hour light/dark cycles were also measured. Results: In iris-CB complexes, glucocorticoid receptor mRNA expression remained stable throughout the day, whereas the mRNA of core clock genes showed a robust circadian rhythmicity. Dexamethasone significantly induced phase-delays when administered between circadian time 8 (CT8) to CT12 and phase-advance when given between CT16 to CT20. Adrenalectomy abolished circadian IOP rhythmicity, particularly diminishing nocturnal IOP elevation compared with sham-operated mice. Conclusions: Glucocorticoids are sufficient for phase shifting the circadian clock in iris-CB. Intact adrenal function is required for manifest circadian rhythms of IOP in mice. Taken together, these data are consistent with the hypothesis that glucocorticoids mediate circadian entrainment of IOP to the master circadian oscillator.

Modulation of iris sphincter and ciliary muscles by urocortin 2.

Urocortin 2 (UCN2) is a peptide related to corticotropin-releasing factor, capable of activating CRF-R2. Among its multisystemic effects, it has actions in all 3 muscle subtypes. This study's aim was to determine its potential role in two of the intrinsic eye muscle kinetics. Strips of iris sphincter (rabbit) and ciliary (bovine) muscles were dissected and mounted in isometric force-transducer systems filled with aerated-solutions. Contraction was elicited using carbachol (10(-6) M for iris sphincter, 10(-5) M for ciliary muscle), prior adding to all testing substances. UCN2 induced relaxation in iris sphincter muscle, being the effect maximal at 10(-7) M concentrations (-12.2 % variation vs. control). This effect was abolished with incubation of indomethacin, antisauvagine-30, chelerytrine and SQ22536, but preserved with L-nitro-L-arginine. In carbachol pre-stimulated ciliary muscle, UCN2 (10(-5) M) enhanced contraction (maximal effect of 18.2 % increase vs. control). UCN2 is a new modulator of iris sphincter relaxation, dependent of CRF-R2 activation, synthesis of prostaglandins (COX pathway) and both adenylate cyclase and PKC signaling pathways, but independent of nitric oxide production. Regarding ciliary muscle, UCN2 enhances carbachol-induced contraction, in higher doses.

Histopathological trabecular meshwork remodeling after cataract surgery detected with an advanced image analyzer.

PURPOSE: To compare the histopathological morphometry of the trabecular meshwork and ciliary processes in pseudophakic eyes and phakic eyes using advanced image analyzer technology. SETTING: McGill University, Montreal, Quebec, Canada. DESIGN: Retrospective case series. METHODS: Thirty-five pseudophakic eyes and 25 phakic eyes were sectioned and converted into digital slides. The total trabecular meshwork area and the ciliary body stroma were demarcated. The area of the trabecular meshwork, cellular and noncellular trabecular meshwork compartments, trabecular space, distance from scleral spur to inner uveal trabecular portion, and degree of fibrosis of the ciliary processes were evaluated. RESULTS: The trabecular meshwork area was larger in the pseudophakic group than the phakic group (P = .03). Furthermore, a trend of larger trabecular space recorded was seen in the pseudophakic group than the phakic group (P = .14). No differences in the proportion of cellular (P = .88) and noncellular trabecular meshwork compartments (P = .4) were seen between groups. The scleral spur to inner uveal trabecular portion distance was longer in the pseudophakic group than the phakic group (P = .008) and correlate with the trabecular meshwork area (P = .0001, r = 0.56). In the ciliary processes, a higher degree of fibrosis was measured in the pseudophakic group than the phakic group (P = .02). CONCLUSIONS: There were significant histopathological changes in the trabecular meshwork and higher fibrosis in the ciliary processes in pseudophakic eyes compared with phakic eyes. These findings support the hypothesis that trabecular meshwork remodeling after cataract surgery is involved in lowering intraocular pressure.

Light entrainment of the murine intraocular pressure circadian rhythm utilizes non-local mechanisms.

PURPOSE: Intraocular pressure (IOP) is known to have a strong circadian rhythm, yet how light/dark cycles entrain this rhythm is unknown. The purpose of this study was to assess whether, like the retina, the mammalian ciliary body and IOP clocks have an intrinsic ability to entrain to light/dark cycles. METHODS: Iris-ciliary body complexes were obtained from period2:luciferase (PER2::LUC) mice and cultured to measure bioluminescence rhythmicity. Pairs of the iris-ciliary body complex were exposed to antiphasic 9:15 h light/dark cycle in vitro. After 4 days of exposure to light/dark cycles, bioluminescence was recorded to establish their circadian phases. In addition, pairs of the iris-ciliary body complex co-cultured with the retinas or corneas of wild-type mice were also investigated. The IOP circadian changes of free-running Opn4-/-;rd1/rd1 mice whose behavior was antiphasic to wild-type were measured by a rebound tonometry, and compared with wild-type mice. Opn3, Opn4, and Opn5 mRNA expression in the iris-ciliary body were analyzed using RT-PCR. RESULTS: The iris/ciliary body complex expressed Opn3, Opn4, and Opn5 mRNA; however, unlike in retina and cornea, neither the iris-CB complex nor the co-cultured complex was directly entrained by light-dark cycle in vitro. The diurnal IOP change of Opn4-/-;rd1/rd1 mice showed an antiphasic pattern to wild-type mice and their rhythms followed the whole-animal behavioral rhythm. CONCLUSIONS: Despite expressing mRNA for several non-visual opsins, circadian rhythms of the iris-ciliary body complex of mice do not entrain directly to light-dark cycles ex vivo. Unlike retina, the iris/ciliary body clocks of blind mice remain synchronized to the organismal behavioral rhythm rather than local light-dark cycles. These results suggest that IOP rhythm entrainment is mediated by a systemic rather than local signal in mice.

Non-invasive measurements of the dynamic changes in the ciliary muscle, crystalline lens morphology, and anterior chamber during accommodation with a high-resolution OCT.

PURPOSE: The purpose of the study was to assess non-invasively the changes in the anterior chamber eye, crystalline lens morphology, and ciliary muscle during accommodation by means of an anterior chamber optical coherence tomographer (OCT), and correlate them with vergence. METHODS: Twenty-five eyes of twenty-five healthy subjects, whose mean age was 29.9±7.1 years, were included and measured with an anterior chamber OCT. The central corneal thickness (CCT), anterior chamber depth (ACD), anterior crystalline lens radius of curvature (ALRC), crystalline lens thickness (CLT), and ciliary muscle area (CMA) were measured for each participant at 0, -1, -2, and -3 D of target vergence. A linear model was used to assess the correlation of each eye parameter with the vergence demand. RESULTS: The mean CCT showed no change for all the accommodative stimuli. The mean ACD and ALRC decreased with the vergence, about 4.5 and 30 % at -3 D, respectively. On the contrary, the CLT and CMA showed an opposite tendency, where the mean CLT was increased by 4.0 % and the mean CMA was done by 26% at -3 D. Statistical significant differences (p < 0.001) were obtained among all vergences for each eye metric, except for the CCT (p = 0.76). CONCLUSION: The ACD and ALRC decreased about 2 and 10 % per dioptre of accommodation, respectively; whereas the CLT and CMA increased about 2 and 9 %, respectively. These results add knowledge regarding the understanding of accommodation and give new perspectives for biomechanics and biometry.

Safety of Using Matrix Metalloproteinase Inhibitor in Experimental Glaucoma Filtration Surgery.

We evaluated the safety of matrix metalloproteinase (MMP) inhibitor in experimental glaucoma filtration surgery in an animal model. Fifteen New Zealand white rabbits underwent an experimental trabeculectomy and were randomly allocated into 3 groups according to the adjuvant agent: no treatment group (n = 5), 0.02% mitomycin C (MMC) soaking group (n = 5), and MMP inhibitor (ilomastat) subconjunctival injection group (n = 5). Slit lamp examination with Seidel testing, pachymetry, and specular microscopy was performed preoperatively and postoperatively. The conjunctiva and ciliary body toxicity were evaluated with scores according to the pathologic grading systems. Electron microscopy was used to examine the structural changes in cornea, conjunctiva, and ciliary body. In the ilomastat-treated group, there was no statistically significant change in central corneal thickness preoperatively and at 28 days postoperatively (P = 0.655). There were also no significant changes in specular microscopy findings over the duration of the study in the ilomastat-treated group. The conjunctival toxicity score was 1 in the control group, 1.5 in the ilomastat-treated group, and 2 in the MMC-treated group. When assessing ciliary body toxicity scores, the ilomastat-treated group score was 0.5 and the MMC-treated group score was 1.5. Transmission electron microscopy did not show structural changes in the cornea and ciliary body whereas the structural changes were noticed in MMC group. A single subconjunctival injection of MMP inhibitor during the experimental trabeculectomy showed a less toxic affect in the rabbit cornea, conjunctiva, and ciliary body compared to MMC.