Numerical study of the effect of head and eye movement on progression of retinal detachment

Rhegmatogenous retinal detachment (RD) is a sight threatening condition. In this type of RD a break in the retina allows retrohyaloid fluid to enter the subretinal space. The prognosis concerning the patients’ visual acuity is better if the RD has not progressed to the macula. The patient is given a posturing advice of bed rest and semi-supine positioning (with the RD as low as possible) to allow the utilisation of gravity and immobilisation in preventing progression of the RD. It is, however, unknown what external loads on the eye contribute the most to the progression of a RD. The goal of this exploratory study is to elucidate the role of eye movements caused by head movements and saccades on the progression of an RD. A finite element model is produced and evaluated in this study. The model is based on geometric and material properties reported in the literature. The model shows that a mild head movement and a severe eye movement produce similar traction loads on the retina. This implies that head movements—and not eye movements—are able to cause loads that can trigger and progress an RD. These preliminary results suggest that head movements have a larger effect on the progression of an RD than saccadic eye movements. This study is the first to use numerical analysis to investigate the development and progression of RD and shows promise for future work.     

Local production of fibronectin by ectopic human retinal cells

Summary The distribution of fibronectin mRNA and fibronectin in adult human retina and epiretinal membranes was investigated by in situ hybridisation and immunohistochemical techniques. The cells in normal adult retina contained little or no fibronectin mRNA and the retina only showed fibronectin immunoreactivity in retinal vessels. The cells in detached neuroretina did not contain fibronectin message but the vitreoretinal interface of the detached retina exhibited variable fibronectin immunoreactivity. Retinal glia, retinal pigment epithelium and fibroblast-like cells in membranes at the vitreoretinal juncture (epiretinal membranes) showed variable labelling with the fibronectin mRNA probe and all the membranes immunostained for fibronectin. No difference could be detected between membrane cell types in the intensity of labelling with the mRNA probe or for fibronectin immunoreactivity. The results indicate that cells in situ in attached and detached adult human retina do not produce fibronectin. Although fibronectin at the vitreoretinal juncture in retinal detachment is probably partly derived from plasma fibronectin resulting from breakdown of the blood-retinal barrier, ectopic retinal cells produce fibronectin and contribute to the glycoprotein in epiretinal membranes.     

Lack of collagen XVIII/endostatin results in eye abnormalities

Mice lacking collagen XVIII and its proteolytically derived product endostatin show delayed regression of blood vessels in the vitreous along the surface of the retina after birth and lack of or abnormal outgrowth of retinal vessels. This suggests that collagen XVIII/endostatin is critical for normal blood vessel formation in the eye. All basement membranes in wild-type eyes, except Descemet's membrane, showed immunogold labeling with antibodies against collagen XVIII. Labeling at sites where collagen fibrils in the vitreous are connected with the inner limiting membrane and separation of the vitreal matrix from the inner limiting membrane in mutant mice indicate that collagen XVIII is important for anchoring vitreal collagen fibrils to the inner limiting membrane. The findings provide an explanation for high myopia, vitreoretinal degeneration and retinal detachment seen in patients with Knobloch syndrome caused by loss-of-function mutations in collagen XVIII.     

Evisceration of Mouse Vitreous and Retina for Proteomic Analyses

While the mouse retina has emerged as an important genetic model for inherited retinal disease, the mouse vitreous remains to be explored. The vitreous is a highly aqueous extracellular matrix overlying the retina where intraocular as well as extraocular proteins accumulate during disease.^1-3 Abnormal interactions between vitreous and retina underlie several diseases such as retinal detachment, proliferative diabetic retinopathy, uveitis, and proliferative vitreoretinopathy.^1,4 The relative mouse vitreous volume is significantly smaller than the human vitreous (Figure 1), since the mouse lens occupies nearly 75% of its eye.⁵ This has made biochemical studies of mouse vitreous challenging. In this video article, we present a technique to dissect and isolate the mouse vitreous from the retina, which will allow use of transgenic mouse models to more clearly define the role of this extracellular matrix in the development of vitreoretinal diseases.     

On the predominance of anti-compensatory eye movements in vestibular nystagmus

The predominance of anti-compensatory eye movements in vestibular nystagmus recorded during sinusoidal and post-rotational tests is interpreted in terms of a mathematical model of the vestibulo-ocular system. Namely, a direct pathway between the vestibular nuclei and the saccadic mechanism is assumed. In the range of frequencies of natural head movements this pathway carries on a signal proportional to head angular velocity. Therefore, during active head movements the saccadic mechanism is forced to produce quick eye rotations in the direction of head movement and, thus, to cooperate in the task of picking up visual targets outside the visual field. During passive head movements giving rise to nystagmus the assumed pathway contributes to reduce the error in eye resetting due to the saccadic delay. Analytical considerations and simulation results seem to prove the adequacy of the proposed model.Work supported by the National Research Council (C.N.R.), Rome, Italy     

玻璃体视网膜手术治疗先天性视网膜劈裂及其并发症的临床疗效

目的:评价玻璃体视网膜手术治疗先天性视网膜劈裂及其并发症的临床疗效。方法:选择2009年1月-2012年1月于我院进行玻璃体视网膜手术的先天性视网膜劈裂患者30例(42只眼),患者均接受了闭合式睫状体经扁平部三切口入路保留晶状体的玻璃体切割手术,并分析其术前及术后情况。结果:先天性视网膜劈裂患者中发生孔源性视网膜脱离19眼,牵拉性视网膜脱离8眼,玻璃体积血10眼,同时伴有视网膜脱离和玻璃体积血有5眼;在末次随访时视力提高者有36只眼,占85.71%,无提高者有6只眼,占14.29%;术前平均视力为(0.15±0.09),末次随访时平均视力提高至(0.31±0.16),两者平均视力差异具有统计学意义(t=5.649,P0.001);42只眼视网膜解剖结构复位良好,视网膜平伏;OCT检查结果显示,末次随访时黄斑劈裂平均面积(0.22±0.18)mm2,与术前黄斑劈裂平均面积(1.07±0.52)mm2比较,差异有统计学意义(t=10.011,P0.001),黄斑微囊样改变有改善;随访期间5只眼出现并发症,占11.90%,其中2眼术后发生PVR且伴牵拉性视网膜脱离,2只眼发生白内障,1只眼出现玻璃体积血,术后视网膜解剖均复位良好。结论:玻璃体视网膜手术可以帮助患者进行视网膜解剖复位及提高其先天性视网膜劈裂患者视功能,具有良好的临床疗效。     

Investigation of saccadic eye movement effects on the fluid dynamic in the anterior chamber

The aqueous humor (AH) flow in the anterior chamber (AC) due to saccadic movements is investigated in this research. The continuity, Navier-Stokes and energy equations in 3D and unsteady forms are solved numerically and the saccadic motion was modeled by the dynamic mesh technique. Firstly, the numerical model was validated for the saccadic movement of a spherical cavity with analytic solutions and experimental data where excellent agreement was observed. Then, two types of periodic and realistic saccadic motions of the AC are simulated, whereby the flow field is computed for various saccade amplitudes and the results are reported for different times. The results show that the acting shear stress on the corneal endothelial cells from AH due to saccadic movements is much higher than that due to normal AH flow by buoyancy induced due to temperature gradient. This shear stress is higher on the central region of the cornea. The results also depict that eye saccade imposes a 3D complicated flow field in the AC consist of various vortex structures. Finally, the enchantment of heat transfer in the AC by AH mixing as a result of saccadic motion is investigated.     

Transcriptomic Analysis of Human Retinal Surgical Specimens Using jouRNAl

Retinal detachment (RD) describes a separation of the neurosensory retina from the retinal pigmented epithelium (RPE). The RPE is essential for normal function of the light sensitive neurons, the photoreceptors. Detachment of the retina from the RPE creates a physical gap that is filled with extracellular fluid. RD initiates cellular and molecular adverse events that affect both the neurosensory retina and the RPE since the physiological exchange of ions and metabolites is severely perturbed. The consequence for vision is related to the duration of the detachment since a rapid reapposition of the two tissues results in the restoration of vision ¹. The treatment of RD is exclusively surgical. Removal of vitreous gel (vitrectomy) is followed by the removal non essential part of the retina around the detached area to favor retinal detachment. The removed retinal specimens are res nullius (nothing) and consequently normally discarded. To recover RNA from these surgical specimens, we developed the procedure jouRNAl that allows RNA conservation during the transfer from the surgical block to the laboratory. We also standardized a protocol to purify RNA by cesium chloride ultracentrifugation to assure that the purified RNAs are suitable for global gene expression analysis. The quality of the RNA was validated both by RT-PCR and microarray analysis. Analysis of the data shows a simultaneous involvement of inflammation and photoreceptor degeneration during RD.     

Experimental retinal detachment causes widespread and multilayered degeneration in rabbit retina

Retinal detachment remains one of the most frequent causes of visual impairment in humans, even after ophthalmoscopically successful retinal reattachment. This study was aimed at monitoring (ultra-) structural alterations of retinae of rabbits after experimental detachment. A surgical procedure was used to produce local retinal detachments in rabbit eyes similar to the typical lesions in human patients. At various periods after detachment, the detached retinal area as well as neighbouring attached regions were studied by light and electron microscopy. In addition to the well-known degeneration of photoreceptor cells in the detached retina, the following progressive alterations were observed, (i) in both the detached and the attached regions, an incomplete but severe loss of ganglion cell axons occurs; (ii) there is considerable ganglion cell death, particularly in the detached area; (iii) even in the attached retina distant from the detachment, small adherent groups of photoreceptor cells degenerate; (iv) these photoreceptor cells degenerate in an atypical sequence, with severely destructed somata and inner segments but well-maintained outer segments; and (v) the severe loss of retinal neurons is not accompanied by any significant loss of Müller (glial) cells. It is noteworthy that the described progressive (and probably irreparable) retinal destructions occur also in the attached retina, and may account for visual impairment in strikingly large areas of the visual field, even after retinal reattachment.     

Different programming modes of human saccadic eye movements as a function of stimulus eccentricity: Indications of a functional subdivision of the visual field

1. Voluntary saccadic eye movements were made toward flashes of light on the horizontal meridian, whose duration and distance from the point of fixation were varied; eye movements were measured using d.c.-electrooculography.—2. Targets within 10°–15° eccentricity are usually reached by one saccadic eye movement. When the eyes turn toward targets of more than 10°–15° eccentricity, the first saccadic eye movement falls short of the target by an angle usually not exceeding 10°. The presence of the image of the target off the fovea (visual error signal) subsequent to such an undershoot elicits, after a short interval, corrective saccades (usually one) which place the image of the target on the fovea. In the absence of a visual error signal, the probability of occurrence of corrective saccades is low, but it increases with greater target eccentricities. These observations suggest that there are different, eccentricity-dependent modes of programming saccadic eye movements.—3. Saccadic eye movements appear to be programmed in retinal coordinates. This conclusion is based on the observations that, irrespective of the initial position of the eyes in the orbit, a) there are different programming modes for eye movements to targets within and beyond 10°–15° from the fixation point, and b_ the maximum velocity of saccadic eye movements is always reached at 25° to 30° target eccentricity. —4. Distributions of latency and intersaccadic interval (ISI) are frequently multimodal, with a separation between modes of 30 to 40 msec. These observations suggest that saccadic eye movements are produced by mechanisms which, at a frequency of 30 Hz, process visual information. —5. Corrective saccades may occur after extremely short intervals (30 to 60 msec) regardless of whether or not a visual error signal is present; the eyes may not even come to a complete stop during these very short intersaccadic intervals. It is suggested that these corrective saccades are triggered by errors in the programming of the initial saccadic eye movements, and not by a visual error signal. —6. The exitence of different, eccentricity-dependent programming modes of saccadic eye movements, is further supported by anatomical, physiological, psychophysical, and neuropathological observations that suggest a dissociation of visual functions dependent on retinal eccentricity. Saccadic eye movements to targets more eccentric than 10°–15° appear to be executed by a mechanism involving the superior colliculus (perhaps independent of the visual cortex), whereas saccadic eye movements to less eccentric targets appear to depend on a mechanism involving the geniculo-cortical pathway (perhaps in collaboration with the superior colliculus).     

Rhegmatogenous retinal detachment in a patient with choroidal melanoma simulating choroidal detachment: a case report

Background

Ophthalmologists and retina specialists may consider choroidal detachment if patients with rhegmatogenous retinal detachment present with choroidal elevation. That misdiagnosis may lead to inappropriate treatments, development of tumor cell dissemination, and eventual promotion of patient death. We report a case of a patient with rhegmatogenous retinal detachment associated with choroidal melanoma simulating choroidal detachment according to fundus findings.

Case presentation

A 78-year-old Japanese woman with blurred vision in her right eye was referred to our hospital because of rhegmatogenous retinal detachment with complicated atypical choroidal detachment. Her intraocular pressure was normal with clear anterior chamber. Retinal detachment involving the inferior and nasal retina was observed, and a retinal hole was noted in the same quadrant. A small yellowish choroidal elevation was located in the inferonasal site. Gadolinium-enhanced magnetic resonance imaging revealed enhancement corresponding to the elevation, leading to the identification of a choroidal tumor. Enucleation of the patient’s right eye was eventually performed. The enucleated eye histologically demonstrated malignant melanoma.

Conclusions

If hypotony or an inflammatory sign is absent, ophthalmologists should pay attention to the differential diagnosis of choroidal elevations observed in such patients.

     

Changes in leucine uptake in the retina of the hamster after traumatic detachment

Protein metabolism was investigated in detached hamster retinas. By sucking off 0.2 ml of aqueous humor from the anterior chamber through limbic insertion of a 27-gauge needle, a tractional force pulled off the neural retina from the retinal pigment epithelium and created a simple detachment without retinal breaks in the right eyes of the hamsters. The left eyes were left untouched as normal controls and sham controls were induced by simple limbic insertion without suction. The animals were sacrificed at selected intervals of 1, 3, 6, 9, 16, 24, 32 days after the operation. Subsequently, scintillation counting and autoradiography were employed to study retinal protein metabolism using leucine uptake as an index. After tritiated leucine uptake, scintillation counting of radioactive substance indicated that detached retinas had taken in less tritiated leucine than normal controls from day 1 to 6 after the operation, but this change had normalized by day 9. For autoradiography, the change in leucine uptake rate was shown to be different in different layers. All the retinal cells seemed to show a decreased leucine uptake with the exception of the outer nuclear layer, in which leucine appeared to be significantly upregulated. This paper illustrates the patterns of protein metabolism and their change after traumatic detachment as well as their possible recovery.     

Mutations in KCNJ13 cause autosomal-dominant snowflake vitreoretinal degeneration

Snowflake vitreoretinal degeneration (SVD, MIM 193230) is a developmental and progressive hereditary eye disorder that affects multiple tissues within the eye. Diagnostic features of SVD include fibrillar degeneration of the vitreous humor, early-onset cataract, minute crystalline deposits in the neurosensory retina, and retinal detachment. A genome-wide scan previously localized the genetic locus for SVD to a 20 Mb region flanked by D2S2158 and D2S2202. This region contains 59 genes, of which 20 were sequenced, disclosing a heterozygous mutation (484C > T, R162W) in KCNJ13, member 13 of subfamily J of the potassium inwardly rectifying channel family in all affected individuals. The mutation in KCNJ13, the gene encoding Kir7.1, was not present in unaffected family members and 210 control individuals. Kir7.1 localized to human retina and retinal pigment epithelium and was especially prevalent in the internal limiting membrane adjacent to the vitreous body. Molecular modeling of this mutation predicted disruption of the structure of the potassium channel in the closed state located immediately adjacent to the cell-membrane inner boundary. Functionally, unlike wild-type Kir7.1 whose overexpression in CHO-K1 cells line produces highly selective potassium current, overexpression of R162W mutant Kir7.1 produces a nonselective cation current that depolarizes transfected cells and increases their fragility. These results indicate that the KCNJ13 R162W mutation can cause SVD and further show that vitreoretinal degeneration can arise through mutations in genes whose products are not structural components of the vitreous.     

Cultivation of the retinal pigment epithelium in the cavity of the lentectomized eye of newts

A study was made of proliferative activity and transdifferentiation of the cells of retinal pigment epithelium (RPE) cultivated in the cavity of the lensectomized eye of adult newt. Implantation of the newt RPE together with vascular membrane and scleral coat resulted in the regeneration of retina. In this process the character of changes in the proliferative activity of RPE and differentiation of retinal cells were the same as in the regeneration of retina in situ. RPE implanted with the vascular membrane alone, despite a high level of proliferation during the first ten days of cultivation, no differentiated retina was formed. Possible causes of these differences are discussed, and the comparison is made of the data obtained with those on RPE cultivation in vitro. After lens removal, with RPE implants present in the eye cavity, in addition to the regenerated lens, 2-3 extra lenses and retina were formed from the cells of the inner layer of the recipient's dorsal iris. Also some cases were revealed of lens formation from the cells of ventral iris. With a complete detachment of the recipient's retina (an after-effect of transplantation) a second differentiated retina regenerated in situ from the recipient's RPE cells.     

Dissection of Human Vitreous Body Elements for Proteomic Analysis

The vitreous is an optically clear, collagenous extracellular matrix that fills the inside of the eye and overlies the retina. ^1,2 Abnormal interactions between vitreous substructures and the retina underlie several vitreoretinal diseases, including retinal tear and detachment, macular pucker, macular hole, age-related macular degeneration, vitreomacular traction, proliferative vitreoretinopathy, proliferative diabetic retinopathy, and inherited vitreoretinopathies. ^1,2 The molecular composition of the vitreous substructures is not known. Since the vitreous body is transparent with limited surgical access, it has been difficult to study its substructures at the molecular level. We developed a method to separate and preserve these tissues for proteomic and biochemical analysis. The dissection technique in this experimental video shows how to isolate vitreous base, anterior hyaloid, vitreous core, and vitreous cortex from postmortem human eyes. One-dimensional SDS-PAGE analyses of each vitreous component showed that our dissection technique resulted in four unique protein profiles corresponding to each substructure of the human vitreous body. Identification of differentially compartmentalized proteins will reveal candidate molecules underlying various vitreoretinal diseases.     

Experimental analysis of lens-forming capacity in Xenopus borealis larvae

Previously, the only anuran amphibians known to have the capacity to regenerate a lens after lentectomy were Xenopus laevis and Xenopus tropicalis. This regeneration process occurs during the larval life through transdifferentiation of the outer cornea promoted by inductive factors produced by the retina and accumulated inside the vitreous chamber. However, the capacity of X. tropicalis to regenerate a lens is much lower than that of X. laevis. This study demonstrates that Xenopus borealis, a species more closely related to X. laevis than to X. tropicalis, is not able to regenerate a lens after lentectomy. Nevertheless, some morphological modifications corresponding to the first stages of lens regeneration in X. laevis were observed in the outer cornea of X. borealis. This suggested that in X borealis the regeneration process was blocked at early stages. Results from histological analysis of X. borealis and X. laevis lentectomized eyes and from implantation of outer cornea fragments into the vitreous and anterior chambers demonstrated that: (i) in X. borealis eye, the lens-forming competence in the outer cornea and inductive factors in the vitreous chamber are both present, (ii) no inhibiting factors are present in the anterior chamber, the environment where lens regeneration begins, (iii) the inability of X. borealis to regenerate a lens after lentectomy is due to an inhibiting action exerted by the inner cornea on the spreading of the retinal factor from the vitreous chamber towards the outer cornea. This mechanical inhibition is assured by two distinctive features of X. borealis eye in comparison with X. laevis eye: (i) a weaker and slower response to the retinal inducer by the outer cornea; (ii) a stronger and faster healing of the inner cornea. Unlike X. tropicalis and similar to X. laevis, in X. borealis the competence to respond to the retinal factor is not restricted to the corneal epithelium but also extends to the pericorneal epidermis.     

Birdshot retinochoroidopathy

Birdshot retinochoroidopathy is a rare bilateral ocular disorder which typically affects healthy, middle-age caucasians. The typical symptoms are recent onset of bilateral floaters with decreased vision in a white and quiet eye. Minimal anterior chamber reaction, vitreous infiltration without snowballs, and multifocal depigmented lesions in the outer retina and choroid are characteristic of birdshot retinochoroidopathy. Other associated findings include retinal vasculitis, paravascular hemorrhage, vitreous hemorrhage, cystoid macular edema, cellophane maculopathy, posterior subcapsular cataract, optic disc edema, vascular attenuation and tortuosity, optic atrophy and retinal or choroidal neovascularization. Management involves Amsler grid self-assessment and routine funduscopic examinations. A recently documented case of treatment with aromatic retinoids showed improvement while many other commonly prescribed medications are equivocal in effect. Laser photoablation or panretinal photocoagulation are recommended for treatable choroidal or retinal neovascularization, respectively.     

Morphogenesis of the eye of Siberian sturgeon

The most relevant changes in Acipenser baeri eye organization were detected between hatching and 5 days post hatch. At this age, the eye had an anterior chamber, lens, iris, choroid gland, scleral cartilage, cornea and a vitreous chamber lined by the retina (with two photoreceptors: rods and single cones).     

兔眼孔源性视网膜脱离手术复位后视功能以及超微结构的变化

目的对比研究兔眼视网膜脱离后选择不同时期手术复位视功能的变化情况,为临床手术时机的选择及预测术后视功能的恢复情况提供理论与实验依据。方法利用家兔制备孔源性视网膜脱离模型,成模后1 d、7 d1、4 d时经手术达解剖复位,采用多焦视网膜电流图检测复位后视网膜的功能,数据处理应用SPSS软件。制备组织病理学切片。结果多焦视网膜电流图显示1 d、7 d、14 d的RRD手术复位后P1波平均象限反应密度(QAP1,nV/deg2),P1波幅值(AP1,μV),N1波幅值(AN1,μV),P1波潜伏期(TP1,ms),N1波潜伏期(TN1,ms)各项数值差异有显著性(P<0.05)。光镜电镜显示视网膜脱离复位后组织病理学改变。结论视网膜脱离手术复位后视网膜细胞功能的恢复与脱离时间有明显的负相关性;多焦视网膜电流图对于局部视网膜功能的评价有重要意义;组织病理学研究提供了解释视功能变化的重要依据。     

Frequency limitations of the two-point central difference differentiation algorithm

A two-point central difference algorithm is often used to calculate the derivative of a function. This estimate is only valid over a limited frequency range. Therefore, the algorithm can be modeled as an ideal differentiator in series with a low-pass filter. The filter cutoff frequency is a function of the time between the points. We discuss the accuracy and limitations of using this algorithm on human saccadic eye movement data. To calculate the velocity of saccadic eye movements the algorithm should have a cutoff frequency of 74 Hz or above.