Increased levels of platelet-derived growth factor in vitreous fluid of patients with proliferative diabetic retinopathy.

UNLABELLED: It is generally accepted that growth factors play an important role in the pathogenesis of proliferative diabetic retinopathy. Since platelet-derived growth factor AB (PDGF AB) is known to be involved in many angiogenetic and proliferative processes, it was the aim of our study to elucidate the role of PDGF AB in the angiogenetic process in proliferative diabetic retinopathy. We measured PDGF AB concentrations in the vitreous of 23 patients with proliferative diabetic retinopathy, 4 of them with additional rubeosis iridis as an indicator of very high vasoproliferative activity. Control measurements were done in 19 patients without diabetic or ischemic eye diseases and also in 4 non-diabetic patients with ischemic proliferative retinopathy with rubeosis iridis. To exclude PDGF remnants in the vitreous due to vitreous bleeding we additionally measured platelet factor 4 concentrations as a stable marker of activated thrombocytes in the vitreous. RESULTS: Significantly elevated concentrations of PDGF AB were found in the vitreous of patients with proliferative diabetic retinopathy, with higher levels in individuals with additional rubeosis iridis compared to controls. However, concentrations of PDGF AB were also elevated in ischemic non-diabetic retinopathy, supporting the concept that ischemia might be a strong stimulator of growth factor production in the retina. Platelet factor 4 was not detectable in any of the vitreous samples included in the study. In summary, our results indicate that the growth factor PDGF plays an important role in the pathogenesis of proliferative diabetic retinopathy, probably in synergistic action with other growth factors like IGF I, IGF II, VEGF and TNF alpha.

[A clinicopathological study of 297 cases of retinoblastoma].

OBJECTIVE: To find a morphological criterion of classification for choroidal invasion of retinoblastoma in order to further study clinical pathology of retinoblastoma (Rb) under an integrate rule. METHODS: The changes of retinal pigment epithelium, Bruch's membrane and choroid on histopathological sections of primarily enucleated eyes with Rb in 297 cases were observed under a light microscope. RESULTS: The globe wall invasion could be morphologically divided into four stages (briefly pigment epithelium-choroid classification). Stage I: Only retinal pigment epithelium was infiltrated, the Bruch's membrane was intact. Stage 2.: The Bruch's membrane was destructed, but the choriocapillaries were not invaded. Stage 3: The invasion reached middle choroidal blood vessels close to the choriocapillaris in a limited scope. Stage 4: Massive choroidal infiltration of all choroidal layers existed and the sclera could be simultaneously involved. The mortality for stage 4 was 11.5% and for stage 1 to 3 was 0.4%. CONCLUSION: The pigment epithelium-choroid stage (PEC-stage) classification in our study can be used as an integrate rule to compare the invasion degree of retinoblastoma in different individuals and studies.

[Morphologic classification of choroidal invasion of retinoblastoma]. / Histomorphologische Stadieneinteilung des infiltrativen Wachstums in der Aderhaut beim Retinoblastom.

In order to inquire into standard for morphologic classification of choroidal invasion of retinoblastoma and to study the tumor clinic--pathologic further under the integrated scale, the changes of retinal pigment epithelium, Bruch's membrane and choroid on the histopathological sectins of 297 cases of primary enucleated eyes of retinoblastoma were retrospectively observed under the light microscopy. The choroidal invasion was morphologically divided into four stages: Stage 1, only retinal pigment epithelium involved, the Bruch's membrane was intact; Stage 2, the Bruch's membrane was destroyed and the choroidal capillaris was not infiltrated; Stage 3, choroial capillary and middle blood vessel layer in small limits were infiltrated; Stage 4, invasion involved in choroid in great limits and involvement of sclera existed simultaneously. This classification (also called pigment epithel--choroid stage, PEC--stage) reflected both infiltrated procedure of tumor cells and preventive mechanism in eye and morphological criterion half--quantitatively. It can be used as a united standard to compare the infiltration degree of retinoblastoma among different individuals and different studies.

Retinal plasma extravasation in animals but not in humans: implications for the pathophysiology of migraine.

High-intensity electrical stimulation of the trigeminal ganglion is accompanied by mast cell degranulation, vasodilatation, increased endothelial permeability and leakage of albumin from postcapillary venules within the dura mater. Overall, the histological appearance suggests an evolving sterile inflammatory response. This neurogenic inflammation within the meninges has been suggested as a model to explain the pain in migraine and cluster headache, and has been used to characterize the pharmacology of anti-migraine compounds. Using the rat model of neurogenic inflammation, the albumin extravasation ratio (stimulated : unstimulated side) in vehicle-treated animals in the dura and retina was 1.60 +/- 0.11 and 1.76 +/- 0.18, respectively (n = 10; values are mean +/- SEM). Pretreatment with sumatriptan (n = 9) produced a highly significant reduction in the ratio of extravasation within the dura to 1.10 +/- 0.06 (P = 0.002) and in the retina to 0.96 +/- 0.06 (P = 0.001), as did the neurokinin-1 receptor antagonist RP 67580 (n = 12) in the dura (1.04 +/- 0.11, P = 0.002) and retina (1.08 +/- 0.06, P = 0.001). These data demonstrate increased endothelial permeability and leakage of albumin not only in the dura but also in the retina. In a second stage we investigated possible extravasation in the human retina in acute migraine (n = 8) and cluster headache (n = 5) using fluorescein or indocyanine angiography. No increased endothelial permeability or leakage of dye could be found in the human retinal or choroidal vessels during headache attacks or in the headache-free interval in persons suffering from both migraine and cluster headache. These data raise the possibility that neurogenic inflammation is not a major factor in headache attacks in migraine or cluster headache.

[Change in hole size and area of retinal detachment after pars plana vitrectomy in Gass stage III macular foramina]. / Anderung der Lochgrösse und des abgehobenen Netzhautbereichs nach Pars-plana-Vitrektomie bei Makulaforamen im Stadium III nach Gass.

UNLABELLED: In 15 patients with a stage III macular hole a pars plana vitrectomy with membrane peeling was performed. At the end of the operation a gas/air exchange was performed and patients had to lie face down for some days. METHODS: Before and 4-7 months after the operation a picture of the posterior pole was taken with a Zeiss fundus camera. Pictures were digitized, and the area of the hole and of the surrounding detached retina was measured using a special image analyzer software. RESULTS: In seven cases an improvement of visual acuity was found; in the remaining eight cases visual acuity remained unchanged. In five cases (33%) the retina was totally attached around the hole. In eight cases the detached area had become smaller, in two cases larger, and in two cases we could no longer observe the rim of the hole. In the remaining cases the area of the holes changes by less than 10%. CONCLUSIONS: The results show that even in cases where total attachment of the surrounded retina cannot be achieved, reduction of the detached area can be expected in most cases. Simultaneously, a reduction of metamorphopsia can be observed. However, the improvement of visual acuity is not very high. That is why we will perform pars plana vitrectomy in stage III holes only in exceptional cases.

[Clinical experiences after implantation of various lens types in silicon oil tamponade]. / Klinische Erfahrungen nach Implantation verschiedener Linsentypen bei Silikonöltamponade.

BACKGROUND: A tamponade of the vitreous space with silicone oil will obligatory lead to cataract after 6 to 12 months. Today it is easily possible, to implant an artificial lense in silicone oil filled eyes. However the combination of an artificial lense and silicone oil will lead to a strong inflammation in the anterior segment of the eye. PATIENTS AND METHODS: 22 pseudophacic patients with silicone oil tamponade were examined 2 to 6 months after the operation. In 12 patients simple artificial lenses were implanted, in 10 patients heparin modified lenses were implanted. In 10 cases the lens was implanted followed by the insufflation of silicone oil in the vitreous cavity, in 2 cases a lens was implanted in a silicone oil filled eye and the silicon oil was not removed. In 8 cases the implantation of the artificial lens has been performed some months to years before the insufflation of the silicone oil. The indication for the silicon oil tamponade was a PVR retinal detachment in all cases. The following parameters were examined: Reaction of the pupil to light, pupil round or oval in miosis, examination of the fundus peripherie possible after mydriasis, fixation of the iris with parts of the capsula or with the anterior surface of the lens? In addition in 12 cases the postoperative refraction was compared with the results of the biometry, which was performed before the operation. RESULTS: In the cases with a simple lens in about 50% an incomplete miosis or an oval pupil because of fixation of the iris with parts of the capsula or with the anterior surface of the lense could be observed. In the cases with heparin modified lenses these complications could be observed in 20%. In all cases a strong opacification of the capsula was seen. In 8 of 12 cases with combined procedure a small hyperopia was measured, in 4 cases a large deviation was measured. CONCLUSIONS: The implantation of an artificial lens in silicone oil filled eyes is an alternative to the aphacic status with an Ando Iridectomy. Obviously heparin modified lenses have advantages in these cases. Because of the strong cataract formation we suggest to remove the anterior and the posterior capsula in the first operative session and to implant the haptics of the lens into the sulcus. Because of the high rate of complications generally first a stable retina condition should be reached before the implanation of an artificial lens is performed.

[Detection and diagnosis of small ocular misalignment with the Purkinje reflex pattern method]. / Nachweis und Diagnose von kleinen Augenfehlstellungen mit dem Purkinje-Reflexmusterverfahren.

BACKGROUND: Application test for an automatic classification strategy for ocular alignment data for the detection of ocular misalignment in strabismic patients. METHODS: Photographic Purkinje Reflection Pattern Evaluation was used a) with a handheld device for the detection and measurement of ocular misalignments in near fixation (group 1, n = 64 strabismic patients) and b) with a stationary device for the detection and measurement of ocular misalignments in near fixation (group 2, n = 38 patients) and in distance fixation (group 3, n = 36 patients). The orthoptic diagnoses were mostly primary and secondary microtropia with manifest angles of strabismus from naught or 0.25 degrees to 3-4 degrees, with maximum angles up to 6-9 degrees. The ocular alignment data were classified using the computer based strabismus index procedure. This strategy relies on thresholds derived from means and standard deviations in orthotropic control populations. In this way the data sets were classified automatically as "no referral" or "referral". In addition, an automatic diagnosis of the type of misalignment was given and the results were compared to the orthoptic gold standard. RESULTS: The sensitivity for the detection of a manifest ocular misalignment was a ca. 80% in group 1 and 2, and 90% in group 3, with specificities from 90% to 100%. All manifest angles of strabismus larger than 1 degree were correctly classified as "referral". There was good agreement between the diagnoses of the type of misalignment in most cases. Discrepancies were observed with very small ocular misalignments or with incomplete data sets, or they could be explained by a switch of fixation. The amount of the misalignment varied markedly as compared to the orthoptic measurement in a number of cases. CONCLUSIONS: The examination allows for a detection of small manifest ocular misalignments with a very high sensitivity. The deviated eye and the type of the misalignment in the primary position are evaluated automatically by a data base computer algorithm. The differences between the measured angles of strabismus indicate that the photographic examination conditions and the orthoptic simultaneous prism and cover test conditions are not exactly alike. Purkinje Reflection Pattern Evaluation represents a step towards an examiner-independent measurement of the angle of strabismus.

Statistical validation of a strabismus index calculated from objective ocular alignment data.

PURPOSE: Statistical analysis of a strabismus index used for objective interpretation of eye alignment data and improvement of this strabismus index. MATERIALS AND METHODS: Primary position eye alignment data of 330 subjects aged from a few months to young adulthood were collected with Purkinje Reflection Pattern Evaluation. Among these there were 95 strabismic subjects with inapparent, very small ocular misalignments from o° to about ±5°. The subjects were split into four age groups: up to 12 months of age, between 12 and 24 months, between 24 and 48 months and above 48 months of age. The measured and calculated angular variables and the strabismus index were tested statistically for age dependence and differences between the three orthoptic groups 'strabismus', 'referral' and 'non-referral'. The level of significance chosen was $aL=0.05. RESULTS: There was a significant dependence of most of the angular variables on the orthoptic group. A dependence of the variables on age was not found except for a few angular variables which seemed to be related to the somewhat larger fluctuations of fixation in the two lower age groups. There was no age dependence of the strabismus index. With a strabismus index threshold of 0.7, the sensitivity was 85% for the detection of cases who needed referral according to the orthoptic examination. CONCLUSIONS: This study provides the statistical basis for the strabismus index procedure which was initially introduced as an empirical procedure. It indicates that the strabismus index does not depend on age, so that limited cooperation in toddlers and infants has no major influence on the result of the data classification with the strabismus index. The strabismus index is a suitable means for objective, examiner-independent decision making in screening for very small ocular misalignment.

Self-assessment of angles of strabismus with photographic Purkinje I and IV reflection pattern evaluation.

BACKGROUND: Accurate assessment of the angle of strabismus, e.g. of variable angles of strabismus, is crucial in preoperative patient management and is usually performed in a clinical environment. Objective assessment by patients themselves, under everyday conditions, could contribute to a better preoperative work-up. A new objective evaluation procedure for the measurement of manifest angles of strabismus for near and distance fixation by the patient himself is presented. METHODS: To account for the modified experimental setup used for the self-assessment, an amended computation procedure of Purkinje reflection pattern evaluation was developed. For measurement, patients and controls placed their head on a head/chin rest and fixated at 33 cm or 4 m distance in primary position. A reflex camera and three photo flash units were positioned on a special frame underneath the visual axis and in front of the subject so that both eyes could be photographed simultaneously. The camera's remote shutter control was released together with the photo flash units by the properly fixating subject. The angles of strabismus were obtained from the series of pictures through later evaluation of the Purkinje I and IV reflection patterns recorded in the photographs of the eyes. RESULTS: Measurements of the ocular alignment in two control groups and in a group of strabismic subjects showed satisfactory accuracy of the "self-assessment" method compared to "standard" Purkinje reflection pattern evaluation and orthoptic measurements of the angle of strabismus. CONCLUSION: The modified "self-assessment" method can be used for the objective recording of angles of strabismus as needed in the preoperative work-up of patients with variable angles of strabismus, over prolonged periods of time, and outside a clinical setting.

Computational principles in Purkinje I and IV reflection pattern evaluation for the assessment of ocular alignment.

PURPOSE: To develop a standardized reasoning for the evaluation of Purkinje I and IV Reflection Pattern data in primary, secondary, and tertiary positions of gaze in the diagnosis of strabismus with a mathematical approach. To demonstrate the applicability of certain mathematical relations and the appropriate graphic representation of computed ocular alignment data. METHODS: Starting from the known Reflection Pattern Evaluation formulae, equations were derived that allowed for the computation of the relative and absolute positions of the optical and visual axes of both eyes from original data in binocular and monocular fixation. These equations were simplified for clinical use. RESULTS: The authors obtained a set of equations that could be applied to the objective, quantitative analysis of eye alignment in screening for microtropia, in concomitant and incomitant diagnoses of strabismus in primary and nonprimary positions. CONCLUSIONS: Purkinje I and IV Reflection Pattern Evaluation can be extended to the diagnosis of strabismus in nonprimary positions with sufficient clinical accuracy. The newly presented principles and equations serve as a basis for a convenient graphic representation of Purkinje I and IV Reflection Pattern data. These principles of evaluation may be applied to any data dealing with ocular alignment, independently of the method.

Measurement of ocular alignment with photographic Purkinje I and IV reflection pattern evaluation.

PURPOSE: To provide reference data for the measurement of ocular alignment and of angles of strabismus with a new stationary photographic apparatus at near and at distance fixation; to verify quantitative relations between the data by comparing experimental data with theoretical predictions. METHODS: Use of Purkinje I and IV Reflection Pattern Evaluation in conjunction with a new stationary photographic apparatus; application of previously derived equations; simulation of angles of strabismus of 5 degrees and 10 degrees in the primary position. RESULTS: Data from 62 subjects with orthotropia show good linearity of measured angles in different directions of gaze; a 95% confidence interval for errors up to 18.6% in the simulated angles of strabismus; no need for individual calibration of the apparatus; no bias due to wearing of spherical corrections, and a detection threshold for microstrabismus of +/- 0.35 degrees. CONCLUSIONS: Data concerning orthotropic and simulated strabismus prove the accuracy of Reflection Pattern Evaluation to assess ocular alignment, for instance, for the diagnosis of strabismus in primary and secondary positions, at near and distance fixation. The measuring range can easily be extended to larger angles of strabismus.

[Examination procedure in automated determination of far and near vision]. / Ein Untersuchungsverfahren zur automatisierten Bestimmung des Fern- und Nahvisus.

BACKGROUND: Although the measurement of visual acuity at distance is more important in ophthalmological practice, the visual acuity at near should be tested additionally. In a recently published paper we showed that with today's computer technology visual acuity at distance can be measured in standardized procedures according to DIN 58220. We describe here an additional, integrated setup, which allows the measurement of visual acuity also at near. METHODS: For testing visual acuity at near, the whole set of optotypes is presented on a transparent overlay mask in front of a computer monitor which is used as a program-controlled light source. A certain optotype is chosen by illuminating its background. The patient's responses are read via a small console by the computer. The test procedure follows the DIN requirements. RESULTS AND CONCLUSIONS: First reliability tests showed that the test arrangement is qualified for rapid and standardized determination of visual acuity at near and at distance under nearly natural viewing conditions.

Retinal hemodynamics after pars plana vitrectomy with silicone oil tamponade.

Pars plana vitrectomy with silicone-oil tamponade is frequently performed in cases of complicated retinal detachment. Because of the lower specific gravity and the lower surface tension of silicone oil in comparison with the aqueous phase of the vitreous, an influence on the blood flow in the retinal vessels would be expected. However, not only the silicone oil but also the operative trauma and a buckling procedure may have an influence on the retinal blood flow. To examine this question we measured the arteriovenous passage time in the silicone-oil-filled eye and in the contralateral eye in 14 cases using a laser scan ophthalmoscope at 3-5 days after surgery. The arteriovenous passage time is a parameter for the retinal microicirculation. In all cases we found a prolonged arteriovenous passage time in the silicone-oil-filled eye in comparison with the contralateral eye (mean value +/- SD, 2.5 +/- 0.8 vs 1.25 +/- 0.25 s; P < 0.01). The prolongation of arteriovenous passage times observed in silicone-oil-filled eyes indicates that the microcirculation is worsened at least during the early postoperative period.

[Computer-assisted measurement of ocular misalignment in infants and young children using the digital Purkinje reflection pattern procedure]. / Computergestützte Messung von Augenfehlstellungen bei Säuglingen und Kleinkindern mit Hilfe des digitalen Purkinje-Reflexmuster-Verfahrens.

A digital image recording and processing system is presented that allows a quick diagnosis of microstrabismus in non-cooperative children. It is thus particularly suited for screening purposes. METHOD: The Purkinje Reflection Pattern Evaluation (RPE) method is used: three small flashes are used to produce the desired Purkinje images. Two horizontal rows of the three 1st Purkinje images (anterior corneal reflections) and of the three 4th Purkinje images (posterior crystalline lens reflections) stemming from the three light sources form the characteristic Purkinje image reflection pattern. Each eye's position is calculated from the shift between the upper and lower rows of reflections by means of two simple formulae. From the angles obtained in binocular fixation and monocular fixation the manifest angle of strabismus corresponding to the angle measured in the simultaneous prism-and-cover test is computed. The measurement is performed at a fixation distance of 50 cm under natural viewing conditions. To obtain a picture one only has to get the child's attention for a short moment. The primary position is triggered with the fixation light, which is operated by a switch. APPARATUS: The digital image recording is done with a hand-held device comprising two miniaturized video cameras, three photo flashes and a fixation light that is operated manually. An IBM-compatible PC equipped with a hard disk and two frame grabbers was adapted for the storage and processing of the pictures. The pictures are evaluated interactively in a few minutes on the workstation's monitor immediately after the measurement. To this end specially designed menu-driven software was implemented. RESULTS: Examples of the measuring procedure and clinical results in infants with microtropic highlight the potential of the system as a screening apparatus and for the exact measurement of small and large squint angles. Usually even 1-year-old children can cooperate well enough to get good-quality pictures in binocular fixation. The new digital system allows easy and rapid application of the Purkinje Reflection Pattern Evaluation method since the time-consuming photographic film processing and evaluation are no longer necessary. For the first time small angles of strabismus under 5 degrees (10 PD) can be measured with a precision of less than 1 degree (2 PD) under clinical conditions in non-cooperative children.

[Extracapsular cataract extraction with phacoemulsification and pars plana vitrectomy with silicone oil tamponade in one session]. / Extrakapsuläre Kataraktextraktion mit Phakoemulsifikation und Pars-Plana-Vitrektomie mit Silikonöltamponade in einer Sitzung.

BACKGROUND: In phacic eyes the development of a cataract is induced by silicon oil. In this case the lens has to be removed in a second operation with or without intraocular lens implantation. In cataract surgery a new incision technique is used, which makes it easily possible to combine both operations in one session. METHODS: A feature of the new incision technique is that a scleral tunnel is dissected before the anterior chamber is opened. The opening closes itself, if the intraocular pressure rises. The danger, that a rise in intraocular pressure during the vitrectomy makes an irisprolaps, for example during the substitution of perfluorcarbon by silicon oil, no longer exists. RESULTS: The operation technique and the postoperative course of three patients with intraocular lens implantation and pars-plana-vitrectomy using silicon oil is reported. CONCLUSIONS: By using the new incision technique in cataract surgery intraoperative complications during vitrectomy like an irisprolaps or penetration of silicon oil into the anterior chamber no longer exist. In selected cases one operation is saved for the patient.

[Elasticity of capsulorhexis in the animal model]. / Die Dehnungskapazität der Kapsulorhexis im Tiermodell.

A special caliper was designed to determine the stretching capacity of a circular capsulorhexis allowing measurements in 0.02 mm increments. A small capsulorhexis 4.5-6.0 mm in diameter could be stretched 2.7 times; a large capsulorhexis 6.5-8.0 mm in diameter was stretched 2.6 times the original diameter. A smooth circular capsulorhexis is very strong and stabile but also has significant stretching capacity. In a small capsulorhexis, there is the danger that zonular fiber defects or posterior capsular rupture may occur during manual expression, of the nucleus. A large capsulorhexis is more suitable for manual nucleus delivery.

Objective measurement of small angles of strabismus in infants and children with photographic reflection pattern evaluation.

A new photographic method for the precise measurement of the angle of squint in children and infants is presented. The apparatus consists of a reflex camera with three horizontally aligned flashes and a small fixation light. The subjects are photographed while fixating binocularly or monocularly in the primary or secondary position. Six reflections can be seen on the photograph of each pupil. These are the first and fourth Purkinje images of each light source. From the reflection patterns, the squint angle or the angle kappa or alpha can be computed using a simple formula. A vertical angle of strabismus may be calculated from the same photograph using the same principle. Results from orthotropic and strabismic adults and from children are evaluated to establish reference values. Cooperation from the children is generally very good. The accuracy of the new method is between between 2 and 4.5 prism diopters (between 1 degree and 2.5 degrees), depending on the measuring strategy.

[Testing vision in children]. / Visusprüfung bei Kindern.

Measurement of visual acuity in children is more difficult than in adults. Children tend to riet when the threshold is reached and become inattentive. However the exact determination of visual acuity in children is important in some situations (Screening, Amblyopia). In this paper we examined whether an automated procedure is more exact than measurement by an examiner. Three series of experiments were done. In n = 173 we measured visual acuity first by an examiner using an optotype projector and second by an automated procedure (computer, keyboard, television screen). Both, the examiner and the computer used the same test-procedure and threshold criterion (DIN-Norm). The correlation coefficient was 0.84. In n = 53 children (age 4 to 7) visual acuity was measured by an examiner without a special strategy. Afterwards visual acuity was measured by the automated procedure. The correlation coefficient was 0.1. In n = 63 children (age 5-7) visual acuity was measured by an examiner using a strategy and a threshold criterion. Afterwards the automated procedure was used. The correlation coefficient was 0.69. The results show, that without a strategy and defined threshold criterion it is not possible to compare the measurements of visual acuity in different times. An automated procedure presented in this paper guaranties constant test conditions in an optimal way.

[A new photographic method for measuring squint angles in infants and small children]. / Eine neue photographische Methode zur Messung von Schielwinkeln bei Säuglingen und kleinen Kindern.

A new photographic method for measuring squint angles in children and infants is presented. A photographic picture is taken from the subject, using a camera with the three flashes bulle. One flashbulle is placed vertically over the lens, two other flashbulles are placed symmetrically in an angle of 10 degrees beside the middle flash. Six reflections can be seen on the photographic picture in each pupil. (1. and 4. Purkinje Sanson Images of each light source.) The horizontal distance of two reflections is determined by the distance of the flashguns. If the reflection lines in both eyes are symmetrical, there is no squint. If there is a shift, it can be measured on the slide and by using a simple formula the squint angle can be calculated. The accuracy of the method is between 2 and 3 degrees.