Time Course Changes of the Mechanical Properties of the Iris Pigment Epithelium in a Rat Chronic Ocular Hypertension Model.

BACKGROUND: The flow field of aqueous humor correlates to the stiffness of iris pigment epithelium (IPE) which acts as a wall of posterior chamber. We focus on the variations of IPE stiffness in a rat ocular hypertension (OHT) model, so as to prepare for exploring the mechanism of duration of OHT. METHODS: Episcleral venous cauterization (EVC) was applied on one eye of male adult Sprague-Dawley rats to induce chronic high intraocular pressure. According to the duration of OHT (0, 1, 2, 4, and 8 weeks), rats were randomly divided into Gw0, Gw1, Gw2, Gw4, and Gw8. Atomic force microscope (AFM) analysis was applied to test IPE stiffness in three regions: iris root, mid-periphery, and pupillary-margin in each group. Histological changes of IPE were also examined in Gw4 and Gw8. RESULTS: There was an overall growing tendency of IPE stiffness in EVC eye. IPE in EVC eye was significantly stiffer than fellow eye in Gw2, Gw4, and Gw8 (in iris root, mid-periphery, and pupillary-margin, p<0.05). IPE in EVC eye in pupillary-margin was significantly stiffer than iris root in Gw4 and Gw8 (p<0.05). In EVC eye, IPE becomes thinner and IPE cell density decreases. CONCLUSION: IPE stiffness increases gradually with the duration of chronic high intraocular pressure.

Unilateral Pigmented Paravenous Retinochoroidal Atrophy Associated With Presumed Ocular Tuberculosis.

This report describes a case of unilateral pigmented paravenous retinochoroidal atrophy (PPRCA) in a patient with low-grade unilateral intermediate uveitis. A 31-year-old woman, previously diagnosed with intermediate uveitis in the right eye (OD) presented to the clinic. Best-corrected visual acuity was 20/20 OD. Fundus examination, fluorescein angiography, autofluorescence, and optical coherence tomography OD were in keeping with a phenotypic diagnosis of PPRCA. Electrophysiology showed severe photoreceptor dysfunction of both the rod and the cone systems OD. Systemic workup revealed QuantiFERON-gold positive. This is the first report of unilateral PPRCA secondary to presumed ocular tuberculosis. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:345-349.].

A comparison of some organizational characteristics of the mouse central retina and the human macula.

Mouse models have greatly assisted our understanding of retinal degenerations. However, the mouse retina does not have a macula, leading to the question of whether the mouse is a relevant model for macular degeneration. In the present study, a quantitative comparison between the organization of the central mouse retina and the human macula was made, focusing on some structural characteristics that have been suggested to be important in predisposing the macula to stresses leading to degeneration: photoreceptor density, phagocytic load on the RPE, and the relative thinness of Bruch's membrane. Light and electron microscopy measurements from retinas of two strains of mice, together with published data on human retinas, were used for calculations and subsequent comparisons. As in the human retina, the central region of the mouse retina possesses a higher photoreceptor cell density and a thinner Bruch's membrane than in the periphery; however, the magnitudes of these periphery to center gradients are larger in the human. Of potentially greater relevance is the actual photoreceptor cell density, which is much greater in the mouse central retina than in the human macula, underlying a higher phagocytic load for the mouse RPE. Moreover, at eccentricities that correspond to the peripheral half of the human macula, the rod to cone ratio is similar between mouse and human. Hence, with respect to photoreceptor density and phagocytic load of the RPE, the central mouse retina models at least the more peripheral part of the macula, where macular degeneration is often first evident.

Effects of simvastatin on retinal structure and function of a high-fat atherogenic mouse model of thickened Bruch's membrane.

PURPOSE: To determine the effect of a statin (simvastatin) on the ultrastructure and function of the RPE, Bruch's membrane (BM), and photoreceptor interface in a high-fat atherogenic mouse model of thickened BM. METHODS: Wild-type C57BL/6 mice (6-weeks old) were divided into three study groups according to their diet and treatment given; Group 1, normal chow diet-fed mice; Group 2, high fat diet (HFD) fed mice; and Group 3, HFD-fed mice treated with simvastatin daily for 30 weeks. All mice were followed-up for 30 weeks. The retinal morphology and function was examined in vivo using fundus imaging and electroretinography at 15- and 30-weeks follow-up. At the end of the study, at 36 weeks of age, eye tissues were collected and retinal sections were examined using light microscopy and transmission electron microscopy. RESULTS: Fundus images of the HFD-fed mice showed the presence of discrete, multiple white spots, which was significantly reduced by approximately 73% in the simvastatin-treated animals. In the HFD-fed mice, there was an increase in the empty cytoplasmic vacuoles of the RPE, presence of lipid droplets in the BM, thickening and fragmentation of the elastic lamina of the BM, and a reduction in retinal function; these ultrastructural and functional changes were significantly improved in the simvastatin-treated group. CONCLUSIONS: Chronic administration of simvastatin significantly improves the ultrastructure and function of the RPE, BM, and photoreceptor in a high-fat atherogenic mouse model of thickened BM.

Functional and anatomic changes in acute multifocal placoid pigment epitheliopathy: a case report.

PURPOSE: To report the functional and anatomic features of a case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE). METHODS: Case report. RESULTS: A 30-year-old man presented with a decrease of visual acuity that started a few days earlier. Fundus examination showed multiple, subretinal, white-yellowish lesions at the posterior pole in both eyes, suggesting APMPPE. Symptoms and clinical signs resolved within a few weeks, leaving well-defined areas of atrophy of the retinal pigment epithelium (RPE). CONCLUSIONS: This case report emphasizes the role of the RPE in the pathogenesis of APMPPE.

Spectral domain optical coherence tomography and in vivo confocal microscopy imaging of a case of Bietti's crystalline dystrophy.

BACKGROUND: The aim was to describe the morphology and localisation of crystals in a case of Bietti's crystalline corneo-retinal dystrophy (BCD) by means of spectral domain optical coherence tomography (SD-OCT) and in vivo confocal microscopy (IVCM). METHODS: Clinical examination, SD-OCT and IVCM evaluation of a 35-year-old woman with BCD. RESULTS: Optical coherence tomography examination of the macular region revealed multiple crystals in the retinal pigment epithelium (RPE)-choriocapillaris, some crystals within the full thickness of the neurosensory retina and less numerous crystals in the choroid. Crystals were present peripherally in areas of retinal atrophy, predominantly in the choroid and to a lesser extent in the RPE-choriocapillaris and the neuroepithelium. In vivo confocal microscopy showed multiple crystals of varying morphology in the peripheral and paralimbal cornea, mainly located in the anterior stroma over 360°. CONCLUSIONS: SD-OCT provided greater precision in the localisation of crystals, found mainly in the choroid and RPE-choriocapillaris rather than the neuroepithelium. In vivo confocal microscopy revealed a higher number of crystals compared to those visible using conventional slitlamp biomicroscopy and showed a different crystal morphology.

Relationship between clinical macular changes and retinal function in age-related macular degeneration.

PURPOSE: The aim of this study was to investigate the relationship between clinical macular changes and retinal function in age-related macular degeneration (AMD). METHODS: We recruited 357 participants with visual acuity of better than 20/60 in the study eye, including 64 individuals with normal fundi and 293 AMD participants classified into 12 subgroups based upon the International Classification and Grading System. Visual function in the study eye was assessed using two steady-state tests (achromatic 14 Hz flicker [F14Hz] and isoluminant blue color [BCT]) and two adaptation measurements (cone photo-stress recovery rate [CRR] and rod dark adaptation recovery rate [RRR]). The groups were compared on their average psychophysical measurements and ranked according to functional deficiency. RESULTS: Both adaptation parameters were significantly abnormal when only hard and/or intermediate drusen were evident (compared to controls, P < 0.023) and yielded considerably worse outcomes in cases with more advanced fundus changes (P < 0.001), but provided limited ability to discriminate between these cases (linear trend, CRR t = 0.68, P = 0.50 and RRR t = 1.76, P = 0.08). Steady-state measurements, however, declined gradually along the entire hierarchy of fundus changes (linear trend, F14Hz t = 10.16, P < 0.001 and BCT t = 11.19, P < 0.001) with F14Hz being able to detect significant functional change as early as in the intermediate drusen group, when compared to controls (P = 0.003). CONCLUSIONS: Steady state thresholds (F14Hz and BCT) and clinical signs showed significant concordance across the spectrum of early AMD fundus changes. This suggests that these tests may be an effective tool for monitoring progression of AMD to supplement clinical grading.

Bilateral acute iris transillumination following systemic moxifloxacin for respiratory illness: report of two cases and review of the literature.

PURPOSE: To describe two cases of bilateral acute iris transillumination following systemic administration of moxifloxacin and review the literature. METHODS: Review of clinical records, and review of the literature using the PubMed database. RESULTS: A 75 year-old man and 33 year-old woman presented with bilateral conjunctival injection, photophobia, and atonic, distorted pupils. The symptoms began acutely following a respiratory illness, for which both were treated with moxifloxacin. Both patients demonstrated profound iris transillumination, sectoral posterior bowing of the iris, corneal endothelial pigment dusting, and trabecular meshwork hyperpigmentation. One patient had a cotton-wool spot. A literature review identified 59 previous reports in 5 publications, including 17 patients with no antecedent fluoroquinolone use. CONCLUSIONS: Increased awareness of this recently described clinical entity should lead to a decrease in unnecessary diagnostic evaluations. It is currently unclear whether this disease represents an adverse effect of fluoroquinolone use or a sequela of a systemic illness.

[The role of light in the developement of RPE degeneration in AMD and potential cytoprotection of minocycline]. / Altersbedingte Makuladegeneration: die Rolle von Licht bei der Entstehung degenerativer Veränderungen im menschlichen RPE und möglicher Zell-Schutz durch Minocyclin.

BACKGROUND: Light-induced oxidative stress is an suggested reason for retinal pigment epithelium (RPE) degeneration in age-related macular degeneration (AMD). This study investigates the influence of light on intracellular reactive oxygen species (ROS) and apoptosis in the human RPE and potential cytoprotective effects of the tetracycline antibiotic minocycline. METHODS: Primary human RPE cells were either pre- or post-incubated with minocycline and then exposed to white light or oxidative stress (600 µM, H(2)O(2)). Then viability, induction of intracellular reactive oxygen species (ROS), apoptosis and cell death was determined. Expression of apoptotic BAX and anti-apoptotic Bcl-2 protein and their mRNA were determined by RT-PCR and Western blot analysis. RESULTS: Both light exposure and oxidative stress decreased RPE cell viability and Bcl-2 expression and increased intracellular ROS, apoptotic cell death, and BAX expression. Minocycline reduced these effects under certain conditions. CONCLUSIONS: This study demonstrates that minocycline effectively protects human RPE cells against oxidative damage. However, in the light of minocycline's photosensitising properties its potential role in AMD treatment needs further evaluation.

[Pigment epithelial detachment in exudative macular degeneration: clinical characteristics and therapeutic options]. / Pigmentepithelabhebung bei exsudativer Makuladegeneration: Klinische Charakteristika und therapeutische Optionen.

Vascularized pigment epithelial detachment (PE detachment) can be viewed as a special form of occult choroidal neovascularization (CNV) owing to the natural course of the disease, its specific pathogenesis and its response to various forms of treatment. This applies to serous PE detachment associated with both occult CNV and also with retinal angiomatous proliferation (RAP). A tear in the retinal pigment epithelium (RIP) represents a serious complication of vascularized PE detachment and is often associated with acute vision deterioration that not uncommonly also involves massive subretinal hemorrhaging. The pathomechanism underlying the development of RIP has not yet been completely elucidated. The notion that the PED bursts as a result of the increased pressure stands in contrast to the theory that the CNV contracts and causes scarring which in turn causing secondary RIP. Anti-VEGF therapy is currently the preferred treatment. However, the initial stabilization of visual acuity after treatment could not be confirmed in long-term studies and after 2 years visual acuity deteriorated significantly. Furthermore, optimal VEGF treatment regimens have also not been defined and the criteria for repeated treatment have not been established as yet. Presently, visual deterioration and the presence of subretinal and intraretinal exudates seem to indicate that treatment will be effective. Here, high resolution OCT imaging should help to provide further insight into the matter.

[Pathogenetic concepts for pigment epithelial detachment in exudative AMD]. / Pathogenetische Konzepte zur Pigmentepithelabhebung bei exsudativer AMD.

Retinal pigment epithelial detachment (PED) as a specific manifestation in exudative age-related macular degeneration (AMD) may lead to a substantial decrease of central vision. An understanding of important events during the development of PED is necessary for a successful therapeutic intervention. At present the leading pathogenetic theory is that of reduced hydraulic conductivity of Bruch's membrane. The mechanisms underlying this process are caused by increased deposition of lipids, enhanced collagen cross-linking and alteration in the ratio of tissue-dissolving enzymes and their inhibitors. The association of newly formed vessels and an unaltered RPE pump activity can lead to the clinical picture of serous PED during exudative AMD.

Epiteliopatía pigmentaria placoide posterior aguda de presentación atípica / Atypical manifestations of acute posterior placoid pigment epitheliopathy

Caso clínicoVarón de 35 años con disminución brusca de la visión de su OI y antecedentes de proceso pseudogripal. A la exploración se observa una lesión blanco-amarillenta foveal acompañada de desprendimiento de la retina neurosensorial y un quiste subfoveal. Se decide instaurar tratamiento con corticoides vía oral consiguiéndose una mejoría significativa de la agudeza visual en 4 semanas.DiscusiónLa epiteliopatía pigmentaria placoide posterior aguda es una enfermedad que afecta a adultos jóvenes y sanos, que se caracteriza por tener buen pronóstico visual sin la necesidad, en la mayoría de los casos, de tratamiento. Existen casos en los que se manifiesta de forma atípica, en los que consideramos que se tendría que contemplar el tratamiento farmacológico con corticoides(AU)

Clinical caseA 35-year-old male with rapid loss of vision of his left eye. He complained of a flulike syndrome one week before the beginning of the symptoms. At the left posterior pole there was a white-yellowish subfoveal lesion associated with a subfoveal cyst and neurosensory retina detachment. We decided to initiate treatment with systemic corticosteroids and the sight improved after 4 weeks.DiscussionAcute posterior placoid pigment epitheliopathy is a disease that typically affects young and healthy adults. It is generally self-limiting and has good visual prognosis. Sometimes the disease includes atypical features such as serous detachment of the neurosensory retina. In these cases we consider that the use of systemic corticosteroids would be necessary(AU)

Dynamic soft drusen remodelling in age-related macular degeneration.

AIMS: To demonstrate and quantify the dynamic remodelling process of soft drusen resorption and new drusen formation in age-related macular degeneration (AMD) with novel interactive methods. METHODS: Twenty patients with large soft drusen bilaterally and without advanced AMD were imaged at baseline and again at a mean interval of 2 years (40 eyes, 80 images). Each of the 40 serial pairs of images was precisely registered by an automated technique. The drusen were segmented by a user-interactive method based on a background levelling algorithm and classified into three groups: new drusen (only in the final image), resorbed drusen (present initially but not in the final image) and stable drusen (present in both images). We measured each of these classes as well as the absolute change in drusen |D1-D0| and the dynamic drusen activity (creation and resorption) D(new)+D(resorbed). RESULTS: Mean dynamic activity for the right eye (OD) was 7.33±5.50%, significantly greater than mean absolute change (2.71±2.89%, p=0.0002, t test), with similar results for the left eye (OS). However, dynamic activity OD compared with OS (mean 7.33±5.50 vs 7.91±4.16%, NS) and absolute net change OD versus OS (2.71±2.89 vs 3.46±3.97%, NS) tended to be symmetrical between fellow eyes. CONCLUSIONS: Dynamic remodelling processes of drusen resorption and new drusen formation are distinct disease activities that can occur simultaneously and are not captured by change in total drusen load. Dynamic changes occur at rates more than twice that of net changes, and may be a useful marker of disease activity.

Non-mitogenic human acidic fibroblast growth factor reduces retinal degeneration induced by sodium iodate.

PURPOSE: To investigate the protective effects of non-mitogenic human acidic fibroblast growth factor on retinal degeneration induced by NaIO(3) in rats. METHODS: Retinal degeneration was induced in adult male Wistar rats via caudal-vein injection of 1% NaIO(3) at 50 mg/kg. One h after NaIO(3) treatment, the right eyes received intravitreal injection of 2.5 microg nm-haFGF in 10 microL saline and the left eyes received saline alone as vehicle-treated eyes. Retinal function in rats was evaluated by electroretinogram (ERG) before injection and 1, 7, and 21 days postinjection. Additional rat eyes were enucleated 7 and 21 days postinjection, fixed, and processed for histological examination. RESULTS: A model of retinal degeneration in rat was established successfully using NaIO(3) injection. Significant decreases in both ERG a- and b-wave amplitudes were detected in NaIO(3)-injected rats when compared with the normal animals (P < 0.05) on day 7 postinjection. Importantly, at the seventh day after intravitreal nm-haFGF treatment on NaIO(3)-injected rats, the nm-haFGF-treated eyes showed a significant improvement in the ERG amplitudes of both a- and b-waves when compared with vehicle-treated eyes (P < 0.05). In addition, the disruptions of photoreceptor outer segments and the retinal pigment epithelium monolayer were much less frequently observed in the nm-haFGF-treated eyes than the vehicle-treated eyes, and the outer nuclear layer thickness in the nm-haFGF-treated eyes was similar to that of the normal eyes. CONCLUSIONS: Intravitreal delivery of nm-haFGF appears to have neuroprotective effect on retinal degeneration induced by NaIO(3).

[Electrophysiological study of the visual system in experimental pigment dystrophy].

Pigment retinal dystrophy induced by the administration of monoiodacetic acid was characterized by a unilateral inhibition of parameters of all components of not only electroretinography, but also evoked potentials of the visual cortex and superior colliculus: higher thresholds of their formation relatively to the controls, and displacement of saturation areas towards low intensities. Correlations of retinogeniculocortical and retinocolliculocortical pathways of visal information transmission were ascertained to be an important factor in the mechanism of visual analyzer functioning in certain abnormalities.

Retinal function in best macular dystrophy: relationship between electrophysiological, psychophysical, and structural measures of damage.

PURPOSE: To establish structure-function correlations across the visual field, to investigate disease progression in Best macular dystrophy (BMD), by correlating structural damage with retinal function as assessed by the combination of psychophysics and multifocal electrophysiology. METHODS: Spatial achromatic and chromatic contrast sensitivities (probing red-green and blue-yellow pathways) were assessed using custom-made psychophysical software to evaluate retinal damage in BMD and age-matched control eyes (n = 19 and n = 22, respectively). Neurosensory retinal dysfunction was also evaluated by means of multifocal electroretinography (mfERG). Correlation analysis was performed between functional parameters in BMD, clinical measures, and morphologic data obtained by optical coherence tomography (OCT). RESULTS: Significant peripheral impairment of retinal function, as measured by mfERG and spatial achromatic contrast sensitivity (CS) methods, was found in BMD. Furthermore, changes in thickness of the neurosensory retina, as measured by OCT, and reduced mfERG responses were also indicators of early loss in BMD and often occurred even with preserved visual acuity. Disease duration was significantly correlated with psychophysical deterioration in chromatic and achromatic tasks but not with mfERG measures. Interestingly, partial correlation analysis revealed a significant independent correlation with our CS measures. CONCLUSIONS: Novel topographic achromatic and chromatic CS methods can detect and quantify functional impairment in early stages of BMD, including the involvement of the peripheral retina and the central chromatic pathway, and can provide new pathophysiological information with added value in relation to electrophysiological and structural measures of damage.

Retinal function in X-linked ocular albinism (OA1).

PURPOSE: To characterize retinal function in human recessive X-linked ocular albinism (OA1) across the normal lifespan. METHODS: Retinal function was evaluated in 14 OA1 patients (ages 11 to 71 years) and five obligate carriers (ages 41 to 50 years) and compared to normal controls using full-field and multi-focal electroretinograms (ERG and mERG, respectively) and electro-oculography (EOG). RESULTS: No consistent differences in ERG response parameters were observed when OA1 patients were compared as a group to normal controls. A trend in the direction of better correlations of response parameters with age was, however, observed in OA1. EOG Arden ratios were normal or hypernormal for all patients, but were uncorrelated with age. Central retinal function measured with the mERG suggested a flat response topography with depressed macular function compared to normal controls. CONCLUSIONS: Panretinal function in OA1 is within normal limits at all ages, consistent with previous reports in generalized albinism. The stronger correlations with age in OA1 may suggest a different rate of age-related change in OA1 compared to normal populations, but the precise nature of this change must await an appropriate prospective study. The topography of mERG amplitudes in OA1 is relatively flat across the central retina with a reduction in amplitude in the macular region consistent with anatomical studies demonstrating an underdeveloped macular region in albinism.

[Pathomechanisms for aging of retinal pigment epithelium (RPE) and prophylactic therapy options in regard to AMD]. / Pathomechanismen der Alterung des RPE und prophylaktische Therapieoptionen im Hinblick auf die AMD.

An intact retinal pigment epithelium (RPE) represents an essential condition for the visual process. This post-mitotic RPE monolayer combines different functions such as degradation of photoreceptor outer segments, vitamin A cycle, support of retinal metabolism and maintenance of the outer blood-retina barrier. As a consequence of excessive metabolism, high oxygen levels, exposition to light of short wave length and ensuing radical formation, the RPE is highly dependent on protective systems. In spite of differentiated defence mechanisms, aging processes cause cumulative RPE damage, representing a major component of age-related macular degeneration (AMD), the leading cause of irreversible severe vision loss in people over 50 years old. A better understanding of the underlying pathophysiology will help to develop new prophylactic options which is becoming more and more important with increasing life expectancy.

Retinal sensitivity measured with the micro perimeter 1 after resolution of central serous chorioretinopathy.

PURPOSE: To examine retinal sensitivity in the macular area of eyes with resolved central serous chorioretinopathy (CSC). DESIGN: Retrospective chart review. METHODS: We studied retrospectively the medical records of 21 patients (21 eyes) with resolved CSC. Using spectral-domain optical coherence tomography (SD-OCT), 6 x 6-mm areas of macula were examined with 256 sequential horizontal scans. Microperimetry in the macular area was performed with the Micro Perimeter 1 (Nidek, Vigonza, Italy). Seventy-two measurement points were located within the central 10 degrees of the macula. RESULTS: In eyes with resolved CSC, most OCT images showed a physiologically normal appearance. However, irregularities of the retinal pigment epithelium (RPE) were detected in 11 eyes, and focal defects of the junctions between inner and outer segments (IS/OS) of the photoreceptors were noted in 15 eyes. These abnormalities often were seen within the foveal region. At 983 (79.8%) of 1,232 points with intact retina, retinal sensitivity was 16 decibels (dB) or better. However, a retinal sensitivity of 16 dB or better was obtained at 34.0% of points with irregular RPE and in 20.0% of points with defects of the IS/OS. The mean retinal sensitivities within the area with irregular RPE (13.4 +/- 4.8 dB) or with defects of the IS/OS (11.5 +/- 4.2 dB) were significantly lower than that of intact retina (17.5 +/- 2.4 dB; P < .0001). CONCLUSIONS: Eyes with resolved CSC often show focal areas with reduced retinal function, which are consistent with irregularity of the RPE or with defects of the IS/OS.