First aid therapy for corrosive chemical eye burns: results of a 30-year longitudinal study with two different decontamination concepts.

PURPOSE: There is currently uncertainty about the most efficacious decontamination solution for corrosive chemical eye burns. This 30-year longitudinal study evaluated the relative efficacy of two different decontamination methods. Passive decontamination consists of rinsing with tap water, 0.9% normal saline, isotonic buffered phosphate solution, or Ringer's lactate. Active decontamination adds an amphoteric, polyvalent, and chelating component with Previn® (Diphoterine®) solution (Laboratoire Prevor, Valmondois, France). METHODS: A prospective evaluation of patients treated in two specialized eye clinics for eye burns was begun in 1988. Recorded data included exposure circumstances, type of corrosive, different types of first therapy, and clinical treatment and outcome. Patients were treated from clinic admission and up to 24 h after the corrosive chemical burn with rinsing for 15 min using two different protocols. From 1988 to 2005, sterile 0.9% normal saline or Ringer's lactate was used. Since 2006, sterile, hypertonic, amphoteric Previn® solution was used. Comparative statistical analysis was done with the Fisher contingency tables and Wilcoxon tests. RESULTS: There were a total of 1495 patients with 2194 chemically burned eyes. In 1988-2005, the annual incidence was 66.1/year; in 2006-2017, it was 65.5/year. Similar incidences were noted when initial rinsing was with tap water or isotonic buffered phosphate solutions. There was a significantly more severe outcome of corrosive chemical eye burns with any first aid rinsing solutions other than Previn® solution or tap water was used (p < 0.001). Previn® solution or tap water rinsing in the pre-hospital setting and secondary rinsing with Previn® solution in the hospital decreased lesion severity in comparison with all other rinsing solutions (p < 0.001). CONCLUSION: The frequency of corrosive chemical eye burns was comparatively high despite tightening of occupational health and safety regulations over the past 30 years. The severity of corrosive chemical eye burns has been dramatically decreased since the introduction of Previn® solution for initial and secondary rinsing. A new protocol for immediate Previn® solution use by the Cologne Fire Brigade and secondary Previn® solution rinsing in hospital has reduced the frequency of severe corrosive chemical eye burns to less than 60% as compared to the period of 1988-2005 when other rinsing solutions were utilized.

[HES 130 as a continuous supplement for organ culture of human corneas?]. / HES 130 als Dauerzusatz in der Organkultur humaner Hornhäute?

BACKGROUND: During organ culture, corneas swell and have to be de-swollen prior to transplantation using a medium. Both swelling and de-swelling lead to increased endothelial cell loss. Furthermore, dextran, the standard de-swelling substance, is toxic and deposited in the cornea. Whether HES is suitable as a continuous supplement for organ culture and keeps the corneas thin was investigated in this study. METHODS: Forty-five human corneas were stored in MEM plus 7.5% HES 130 for 7, 15, 21, and 28 days. Endothelial cell count was determined before and after organ culture. After storage the water content and amount of adenosine phosphates were measured. RESULTS: Water content was 82.29% after 7 days, 82.98% after 15 days, 81.15% after 21 days, and 83.21% after 28 days. The endothelial cell count decreased by 1.20% after 7 days, 0.60% after 15 days, 4.29% after 21 days, and 6.89% after 28 days. ATP was 0.159 micromol/g dry weight after 28 days of organ culture. CONCLUSION: The water content of corneas stored in HES-containing medium remained constant even after 21 days of organ culture. Endothelial cell loss was less than in comparable studies using a standard medium containing 10% FCS; however, ATP concentrations were worse. HES 130 keeps the corneas thin and can be used as a continuous supplement. It facilitates the handling of corneas during organ culture, making dehydration before transplantation unnecessary, and thus also reduces potential stress factors for the cornea.

Quantification of retinal capillary density and flow velocity in patients with essential hypertension.

Arterial hypertension is known to be an important risk factor for cerebral and cardiovascular disease. Previous studies in rats have demonstrated that changes in both capillary density and vessel diameter may contribute to increased vascular resistance in hypertension. In vivo studies of human subjects with essential hypertension revealed a reduction in the number of arterioles in the skin and conjunctiva; no other in vivo data are available from other tissues. By means of a new imaging technique, capillary density and capillary blood flow velocity can now be assessed in the human retina. We undertook the present investigation to determine whether patients with essential hypertension and only minor clinical retinal vascular alterations have decreased retinal capillary density and altered capillary flow velocity. Seventeen hypertensive patients with only minor retinal vascular alterations and 17 healthy volunteers matched for age were selected. All study participants underwent ophthalmologic examination and fluorescein angiographic studies by means of scanning laser ophthalmoscopy. Capillary density and capillary blood flow velocity in the perifoveal network were evaluated from the angiograms. The retinal microcirculation in the perifoveal capillary network of hypertensive patients showed significant alterations. Both the capillary density and capillary flow velocities were significantly reduced compared with the control group. For the first time alterations of capillary blood flow and capillary density in a vascular network very similar to that of the brain have been demonstrated in hypertensive patients in vivo. Further studies with this technique may help identify patients at high risk for cerebrovascular diseases.

The influence of the cause of death and age on human corneal metabolism.

PURPOSE: Little is known about the metabolic status of human corneas before transplantation. The authors attempted to determine the influence of both cause of death and age on the corneal metabolism. METHODS: Adenosine-triphosphate (ATP), adenosine-diphosphate (ADP), glucose, and lactate were measured in the stroma and endothelium of 30 human corneas. The corneas were divided into four groups according to cause of death and four groups according to age. Corneas from donors with diabetes were excluded. RESULTS: Corneas from patients who died suddenly--because of cardiac infarction, for example--have good metabolic status even 24 hours after death. In corneas of patients with cancer or sepsis, the metabolism has run down. In comparison, corneas from patients with cancer are in better metabolic condition than those from donors with sepsis because they have adapted to catabolism. Corneas donated from patients with renal insufficiency show results somewhere in between. Statistical evaluation revealed significant differences in ATP concentrations for corneas from donors who died suddenly and from patients with renal insufficiency compared to corneas from patients with sepsis. It could be shown that glucose concentrations as a resource for metabolism increase with age. The best ATP-ADP ratios were found in the group of 40- to 59-year-old donors. Nevertheless, differences between the age groups were not statistically significant. CONCLUSION: From our results it can be concluded that the cause of death and systemic metabolism have an influence on corneal metabolism. Results concerning donor age reflect the well-known fact that donor age has no influence on the quality of keratoplasty material.

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.

Quantification of cystoid changes in diabetic maculopathy.

PURPOSE: In patients with diabetic macular edema and cysts, quantification of the extent of the cystoid formation has been difficult. This study was performed to introduce reliable measurements of cysts, the quantification of the extent, and its relation to visual acuity. METHODS: Fluorescein angiography generated with a scanning laser ophthalmoscope provided detailed recognition not only of the foveal microvasculature, but also of well-demarcated cystoid formations in the early phases. The sampling area included the central 2.5 degrees of the fovea. Using digital image analysis, two independent observers estimated the area covered by cysts, the number of cysts, and the foveal avascular zone (FAZ). RESULTS: Twenty-three subjects with diabetes and macular cysts were enrolled in the current study. The mean area of the cysts was 0.315 +/- 0.241 mm2 (0.05 mm2 to 0.9 mm2), and the number of cysts ranged from 1 to 7. Both parameters, area of cysts (r2 = 0.61), and number of cysts (r2 = 0.48) showed a significant correlation with visual acuity (P < 0.01), whereas FAZ (0.08 to 0.58 mm2) showed no significant correlation with visual acuity. CONCLUSIONS: Fluorescein angiography allows a reproducible quantification of the extent of macular cysts. The relation of visual acuity to the number of cysts and to the area covered by the cystoid formation is highly significant. Thus, both these measures can provide an objective criterion for the estimation of visual prognosis and an outcome for evaluation therapy techniques.

The relationship of macular microcirculation to visual acuity in diabetic patients.

OBJECTIVE: To assess the perifoveal microcirculation in diabetic maculopathy without clinically significant macular edema and its relationship to visual acuity. DESIGN: Prospective analysis. SETTING: A teaching hospital. PATIENTS: Fifteen patients with impaired visual acuity of 20/50 or worse, a diabetic control population with unaffected visual acuity (matched age, gender, retinopathy stage), and 52 healthy controls were enrolled. INTERVENTIONS: Study consisted of video-fluorescein angiography with image analyses and hemoglobin A1c measurements. MAIN OUTCOME MEASURES: Macular capillary blood velocity, capillary density (perifoveal intercapillary area), and foveal avascular zone. RESULTS: The capillary blood velocity was significantly reduced in both diabetic groups (P < .001) when compared with healthy controls, but did not differ significantly among the two diabetic groups. The perifoveal intercapillary area and foveal avascular zone were significantly enlarged in both diabetic groups compared with healthy controls (P < .001). The foveal avascular zone (P < .01) and perifoveal intercapillary area (P = .01) were further enlarged in the diabetics with reduced visual acuity. The visual acuity correlated significantly with foveal avascular zone (R2 = .51) and perifoveal intercapillary area (R2 = .24), indicating an association between enlargement and declined visual acuity. CONCLUSIONS: Capillary blood velocity remained unchanged regardless of presence of visual impairment, whereas foveal avascular zone and perifoveal intercapillary area indicated ischemia. This may help in defining a critical hypoxic threshold for visual loss and identifying the presence of an ischemic diabetic maculopathy.

Measurement of retinal hemodynamics with scanning laser ophthalmoscopy: reference values and variation.

High resolution video fluorescein angiography using scanning laser ophthalmoscopy allows the assessment of retinal macro- and microcirculation. Data on the retinal macrocirculation were obtained from 221 healthy subjects. The data were derived from estimations of the arm-retina time, the arteriovenous passage time and mean arterial dye velocity, characterizing the passage of fluorescein to the eye, the mean arterial plasma velocity, and the arteriovenous passage through the entire vascular bed of one segment. Additionally, the transit of hypofluorescent segments in the capillary macular network were measured in 90 healthy subjects. These parameters provide a wide range of information for understanding the physiology of healthy and diseased eyes. Fundamental for all interpretations is the knowledge of the physiological variations. In the present study the inter- and intraindividual variability of retinal hemodynamics in healthy volunteers were assessed. The interindividual variation was 23.8% for the arm-retina time, 20.7% for the arteriovenous passage time, 23.7% for the mean arterial dye velocity, and 14.2% for the capillary flow velocity; the coefficient for variation, characterizing the intraindividual variation, was 26.6%, 15.6%, 16.7%, and 7.9%, respectively. The knowledge of the inter- and intraindividual variation of retinal blood flow indices allows for a priori power estimations for pathophysiologic and pharmacological studies.

Complications of lid surgery.

Fifty-seven patients operated for basal cell carcinoma of the lids were reexamined with regard to postoperative and late complications. Minor immediate complications without long-lasting consequences occurred in 37%. Bad scar formation was seen in 4 out of 57 cases. Four other cases suffered with recurrences. Two of these cases were treated with X-rays several years before the surgical intervention.

Acute effect of metipranolol on the retinal circulation.

AIM: To assess the effect of topical and systemic application of a beta adrenergic receptor blocker on retinal haemodynamics. METHODS: 24 healthy subjects were included in this double masked, randomised, placebo controlled crossover study. Metipranolol, a non-selective beta adrenergic receptor blocking agent was used as test drug. In all subjects arm-retina time, arteriovenous passage time, arterial mean dye velocity, the arterial vessel diameters, and capillary flow velocity were quantified from digital video fluorescein angiograms. RESULTS: A significant effect was observed on the arteriovenous passage time (p < 0.05), the arterial mean dye bolus velocity (p < 0.05), and capillary blood velocity (p < 0.05), but not on the arterial vessel diameter. The arterial mean dye bolus velocity and capillary blood velocity increased after application of the test drug (topical and systemic). In tandem with this a decrease of the arteriovenous passage time was observed. The perfusion pressure increased after topical application and remained unchanged after systemic application of metipranolol. CONCLUSIONS: This study shows that systemic as well as topical application of metipranolol leads to increased retinal blood flow velocities. The implications of these results for treatment with beta adrenergic receptor blockers is not clear. However, in view of these data it is very unlikely that treatment with metipranolol has a negative effect on retinal blood flow.

Retinal microcirculation in patients with diabetes mellitus: dynamic and morphological analysis of perifoveal capillary network.

The new scanning laser technique allows one to quantify the retinal microcirculation. A digital image analysing system was used to study capillary blood flow velocities and morphological parameters of perifoveal intercapillary areas and foveal avascular zones in normal and diabetic subjects. Diabetic patients showed a significant reduction in capillary blood cell velocities in comparison with normal subjects. Perifoveal intercapillary areas and foveal avascular zones were significantly increased in all stages of diabetic retinopathy, and both parameters increased with progressing diabetic retinopathy. Significant changes in the perifoveal intercapillary areas were observed between normal subjects and patients with no retinopathy.

Retinal circulation times in diabetes mellitus type 1.

Video fluorescein angiography was performed in 124 patients between 18 and 65 years of age (mean 35.0, SD 12.3 years) with juvenile-onset, insulin-dependent diabetes mellitus (type 1). The arm-retina time (ART) and the retinal arteriovenous passage time (AVP) were measured by means of a picture analysis system to quantify the retinal microcirculation. Glucose metabolism was assessed by the blood level of haemoglobin A1c. The ART 11.5, SD 3.4 s) was similar to that in normal persons (11.2, SD 3.3 s), while the AVP was significantly longer in the diabetics (AVP = 2.35, SD 0.87 s) than in normal persons (AVP = 1.45, SD 0.40 s). The patients with severe diabetic retinopathy showed the most impressive change in AVP. The diabetics with good glycaemic control, that is, with glycosylated haemoglobin (HbA1c) less than or equal to 8.0 g/dl, had a shorter AVP than patients with bad glycaemic control (HbA1c greater than or equal to 9.5 g/dl). The group with a history of diabetes for less than five years showed circulation parameters similar to those of normal persons. The AVP in this group was significantly shorter than in groups with a history of diabetes for five or more years.

Macular microcirculation in cystoid maculopathy of diabetic patients.

BACKGROUND: In patients with diabetic macular oedema and central cysts ischaemia of the retina appears to be an important contributing factor in the pathogenesis of cysts. This study was performed to further elucidate the role of the inner retinal microcirculation in diabetic cystoid macular oedema (CMO). METHODS: Video fluorescein angiography allows visualisation of the macular microvasculature and measurements of the capillary blood velocity (CBV), foveal avascular zone (FAZ), and perifoveal intercapillary area (PIA, characterising capillary density). RESULTS: Twenty three diabetic subjects with CMO, matched diabetic patients without macular oedema (n = 23), and healthy subjects (n = 23) were included. CBV, PIA, and FAZ did not differ significantly among diabetic groups regardless of presence of cystoid changes. CBV was significantly reduced (p < 0.0001) and PIA was more than doubled in both diabetic groups (p < 0.0001) when compared with healthy subjects. Furthermore, FAZ showed a nearly doubled size in diabetic patients without macular oedema (p < 0.01) and a less pronounced enlargement (by 29%) in diabetics with CMO (p < 0.05). CONCLUSION: The results indicate that the retinal microcirculation in diabetic patients is markedly altered when compared with healthy subjects, regardless of CMO presence. In CMO patients the microcirculatory changes are similar to those of diabetic patients without macular oedema. Thus inner retinal perfusion does not contribute to tissue ischaemia leading to cystoid formations in diabetic maculopathy.

N-acetylglucose aminidase activity in corneoscleral ulceration after severe eye burns.

In some patients with severe burns, major problems were delayed regeneration of the surface epithelium, extensive ulceration of the sclera near the limbus, subsequent corneal ulceration, and subconjunctival scarring. Human tissues surrounding ulcerations in severe eye burns were obtained from surgical interventions in 12 such patients. High activities of the lysosomal marker enzyme N-acetyl-glucose aminidase were found. As is known from histological examinations, these tissues do not represent regeneration of conjunctiva, but rather inflammatory proliferation. The tissues adjacent to corneoscleral ulceration release large amounts of lysosomal destructive enzymes. The rather simple assay of the activity of the N-acetylglucose aminidase proved useful in clinical cases to assess the activity of the inflammation of eye burns and to estimate the efficacy of the therapy applied.

Remarks on the vitality of the human cornea after organ culture.

The purpose of this study was to obtain further information on the viability of organ-cultured human cornea. We thus used a specific staining method for succinate dehydrogenase (SDH), which is located in the membrane system of vital mitochondria. We examined fresh and long-term-cultured human corneas. After an initial incubation period in dextran-free culture medium, corneas were stored in a medium containing dextran. With respect to different appearances of the SDH staining, minimal essential medium without dextran seems to have a positive effect on the condition of epithelial cells. After renewal of the medium, keratocytes showed a brief improvement followed by a delayed deterioration, while the endothelial cells were severely damaged. However, best results for all three cell types were observed on the fourth day in a medium containing dextran. We therefore conclude that these corneas were best suited for transplantation.

Assessment of conjunctival epithelium after severe burns and surgical reconstruction with Tenon plasty by means of a modified impression cytology procedure.

PURPOSE: Tenon plasty has been used to reconstruct the conjunctival surface in severe burns in which ischemic sclera was exposed or undergoing ulceration. A modified impression cytology procedure was applied to investigate the conjunctival epithelium. The quality of the regenerated epithelium on the advanced Tenon sheets was assessed. METHODS: The 63 conjunctival samples of eye-burn patients were investigated. Among these, 41 patients had very severe bums. Conjunctival samples were collected from 6 weeks after surgery to 5 years after the accident. They were compared with conjunctival epithelia obtained from 53 normal eyes of healthy volunteers. A 25-mm2 Biopore membrane (Millipore Catalogue PICM 01250) was placed on the bulbar conjunctiva surface in the lower temporal quadrant, at a distance of 3-5 mm from the limbus, till it was soaked with fluid. The ablated cell sheets were stained with periodic acid-Schiff (PAS). RESULTS: In all cases, an intact conjunctival epithelium was observed. In healthy eyes, 2,338 epithelial cells/mm2 and 155 goblet cells/ mm2 were found. Eyes after a surgical reconstruction with Tenon plasty resulted only in 1,575 epithelial cells/mm2 and 72 goblet cells/mm2. The differences were highly significant. The ratio of epithelial to goblet cell counts revealed an increase of goblet cells during the postoperative period. CONCLUSION: Conjunctival epithelium as well as goblet cell densities were reduced after heat, lime, alkali, and acid burns. However, after concrete burns, cell densities were increased. Tenon plasty provided the regeneration of the fully intact conjunctival epithelium. Goblet cells were present from 6 weeks after the surgery on; their number increased gradually. The stimulation of the goblet cell mucous secretion is discussed.

A histochemical study of the distribution of dextran 500 in human corneas during organ culture.

PURPOSE: The aim of this histochemical study was to demonstrate the absorption of dextran 500 and its distribution in the cornea after storage under standard eye bank conditions. Furthermore, an attempt was made to distinguish between the soluble and insoluble parts of dextran 500 absorbed by the cornea, in order to see how much dextran remains in the cornea after transplantation. METHODS: Forty-nine fresh and 65 organ-cultured human corneas were investigated. The corneas were cultured for 28 days in a dextran-free medium, followed by a period of 1-14 days in a medium containing 5% dextran 500. Cryosections were stained by aqueous PAS and a modified alcoholic PAS to determine the amount of dextran. RESULTS: Dextran was not found in the epithelium, stroma or endothelium of fresh human corneas. By contrast, extra- and intracellular positive staining reactions were detected in corneas following storage in a medium containing dextran. Dextran 500 absorption was relatively diffuse in the epithelium after storage in a dextran medium. Initial accumulations were found in the stroma near Bowman's and Descemet's membranes and also in the central part of the cornea, as the period of culture in the medium containing dextran lengthened. We also observed interaction between the stroma and endothelium: decreasing amounts in the endothelium were followed by an increase of same in the stroma. Intracellular deposits of dextran were detected after only one day. A much greater part of the extracellular dextran than previously described was found to be insoluble. CONCLUSIONS: As the amount of dextran in the cornea increases over a longer storage time, we conclude that the period of storage in a medium containing dextran should be limited to four days. The fact that the cornea is saturated with dextran after seven days has been shown in further studies to interfere with mitochondrial function and may also cause severe post-operative swelling of the transplant, hence leading to a longer recovery period for the patient.

Survival of corneal grafts after severe burns of the eye.

The authors investigated 32 human corneal buttons of patients suffering from severe eye burns. The keratoplasties were performed in different periods after the burn and collected within five years. Grafts were followed-up until they failed because of ulceration or until rehabilitating keratoplasties were performed. Early (up to six months after the burn) and late (more than 12 months after the burn) obtained corneas showed different cellular reactions in the corneal stroma. Inflammatory cells such as granulocytes and lymphocytes decreased with increasing periods after the burn. More than 12 months after the burn, minor inflammatory cellular reactions but increasing scar formation could be found. Four out of 19 early-, two out of eight intermediate- (between six and 12 months after the burn) and one of the late performed keratoplasties failed and had to be replaced by new corneal grafts. Due to the conditions in the graft beds the explanted corneal grafts showed a cellular reaction in the stroma comparable to the previously explanted burnt corneae. Further complications occurred because of problems concerning the ocular surface. After preliminary therapeutical keratoplasties rehabilitating keratoplasties could be successfully performed in four cases between 19 and 39 months.

Eye burns: an emergency and continuing problem.

Adequate treatment of eye burns is an essential task of rescue teams. Clinical and occupational medicine studies have shown that efficient emergency treatment can prevent severe eye damage, but therapy is frequently delayed or inadequate. When initial therapy has been delayed or missed, several treatment strategies, including surgery, are available that may improve the outcome of an injury with poor visual prognosis. Discussed in this review are common accident mechanisms, causative agents and biophysical/pathogenetic aspects of eye burns, together with emergency and long-term treatment strategies including surgical procedures, and factors influencing outcome.

Comparative study on the effects of chlorite oxygen reaction product TCDO (tetrachlorodecaoxygen) and sodium chlorite solution (NaClO2) with equimolar chlorite content on bone marrow and peripheral blood of BDIX rats.

The effects of the chlorite-oxygen reaction product TCDO (tetrachlorodecaoxygen, active ingredient of the systemic application form of WF 10) were investigated on bone marrow and peripheral blood of BDIX rats in comparison to a sodium chlorite solution with a chlorite content identical to that of WF 10. Despite difficulties in determining the chemical differences between TCDO and a sodium chlorite solution, their differing effects on cells, tissue and organism were striking. The following characteristics have been observed: Stimulation of the bone marrow, evidenced by the pronounced increase in mature granulocytes, pronormo- and normoblasts, or increased cell proliferation rate, determined by means of the BrdUrd method, was achieved only with WF 10 (TCDO). Stimulation of the bone marrow led in turn to increased numbers of leucocytes and monocytes in the peripheral blood. In addition, WF 10 induced the production of large granular lymphocytes (LGLs), referred to as natural killer cells (NK-cells). In contrast, NaClO2 solution suppressed bone marrow function, exhibiting a toxic effect when given on a long-term basis. At the same time the number of mature granulocytes as well as pronormo- and normoblasts decreased, while the presence of LGLs was not observed. The results showed that TCDO is a potent stimulator of the bone marrow function and an effective modulator of the entire immune system. The toxic effect of chlorite, derived from the TCDO matrix, is not noticeable, being completely compensated by the favourable effects of TCDO.