Application of eye drops to the medial canthus

Background: Our purpose was to investigate the efficacy of instillation of eye drops in the medial canthus with the lids closed at the time of application. Methods: The pupils of 50 healthy volunteers were dilated with tropicamide 0.125%. The effect of the drug on pupillary dilatation when instilled in one eye with the lids closed was compared to its effect when instilled in the conventional mode in the other eye. Results: Maximal mydriasis achieved was 2.75 ± 0.76 mm in the eye with closed lids and 2.8 ± 0.77 mm in the eye in which eye drops were instilled in the conventional mode. Conclusion: Eye drop instillation in the medial canthus with the lids closed at the time of application seems to be an effective means of ophthalmic drug delivery.     

The additive miotic effects of dapiprazole and pilocarpine

Background: Since dapiprazole on alpha-adrenergic agent, produces miosis by paralyzing the dilator muscle, and pilocarpine, a parasympathetic drug, causes miosis by affecting the sphincter, we speculated that the two drugs might have additive effects. Methods: The additive miotic actions of pilocarpine 2% and dapiprazole 0.5% were evaluated by comparing the effects of two drugs given together and alone on the reversal of mydriasis induced by tropicamide (0.5%) and phenylephrine (10%) in one eye each of 60 healthy volunteers. Results: Dapiprazole and pilocarpine together induced miosis significantly faster than each drug alone, showing additive effects. Conclusion: Co-administration of dapiprazole and pilocarpine at the end of the eye examination will induce fast pupillary constriction, which might be useful in preventing the development of an acute attack of angle-closure glaucoma in patients with anatomically narrow angles.     

Intracorneal bovine albumin: an immunologic model of corneal angiogenesis

Background: We characterized the neovascularization that follows the intracorneal injection of bovine albumin (BA) in rabbits as a model of corneal angiogenesis. Methods: New Zealand white rabbits received intracorneal injections of phosphate-buffered saline with and without various amounts of BA. The rabbits were co-sensitized or presensitized by intramuscular BA or were not sensitized. The corneal vascular response was quantified by ranking photographs taken periodically after the injection. Results: In pre-sensitized animals, blood vessels were apparent within 4 days and reached maximum intensity 14 days after the intracorneal injection. Corneas also vascularized in nonsensitized rabbits, but a larger dose (>0.2 mg BA) was required than in pre-sensitized animals (>0.02 mg BA). Vascularization began later in non-sensitized animals and was less extensive than in pre-sensitized animals. Conclusion: The intracorneal injection of BA is a reproducible model of corneal angiogenesis in rabbits and should allow the involved immunological mechanisms to be elucidated.     

Influence of oxygen free radicals and free radical scavengers on the growth behaviour and oxidative tissue damage of bovine retinal pigment epithelium cells in vitro

Purpose: This investigation was carried out to ascertain whether oxygen free radicals can influence the growth behaviour and consecutive lipid peroxidation of retinal pigment epithelium (RPE) cells in vitro and whether scavengers can counteract these effects. Methods: The experimental model was based on calf RPE cells. Hypoxanthine/xanthine oxidase (HX/XO) and superoxide dismutase/catalase (SOD/CAT) served as the radical generating system and scavengers, respectively. The components were tested alone and in combination. Lipid peroxides were determined in culture supernatants by a thiobarbituric acid assay. Results: Concentrations of up to 100 mol/1 of HX alone and 500/1000 U of XO alone, as well as the application of the scavengers without the radical generating system (HX/XO), had no effect. Doserelated reduction of cell growth and increase of lipid peroxidation were found with HX/XO treatment (single dose of 500 and 1000 U/ml 24 h after seeding). After application of 500 or 1000 U/ml of XO, CAT, when given alone (1200 U/ ml), counteracted the effect of the radicals on cell growth and lipid peroxidation; SOD (300 U/ml) had no effect. A combination of SOD and CAT was no better than the effect of CAT alone. Conclusion: The prevention of radical-induced reduction of cell growth and lipid peroxidation by scavengers supports trials of therapy using antioxidants and/or free radical scavengers for various ocular syndromes with RPE involvement.     

A comparison of colour Doppler imaging of orbital vessels and other methods of blood flow assessment

Background: Comparison of the haemodynamic measurements obtained by colour Doppler imaging and other methods of ocular blood flow measurements was desired. Methods: The blood velocity findings from colour Doppler imaging of patients with central retinal vein occlusion were compared to the results of fluorescein video-angiography, continuous tonography and ophthalmodynamometry. Results: Patients with low or undetectable blood velocities in the central retinal vein had longer retinal dye transit times on fluorescein video-angiography. Tonography showed a positive correlation with the velocities in the ophthalmic artery, but ophthalmo-dynamometry showed a negative correlation with these velocities. Conclusion: The relationships between the blood velocities in orbital vessels and other blood flow measurements emphasise that there is a complex interaction of the blood flow parameters. Care must therefore be taken when interpreting the results of studies.     

Adult-onset foveomacular vitelliform dystrophy and indocyanine green videoangiography

Background Adult-onset foveomacular vitelliform dystrophy (AOFVD) represents a heterogeneous group of disorders with different clinical, angiography, and histopathological features. The most common form is characterized by a yellow, round to oval subretinal macular lesion with or without central pigmented spot. Methods Eight patients affected by typical AOFVD underwent fluorescein an giography and indocyanine green videoangiography (ICGV). Results Fluorescein angiography showed a central hypofluorescent spot surrounded by an irregular hyperfluorescentring ICGV demonstrated a foveal nonfluorescent spot, visible during the entire examination, and a hyperfluorescent area surrounding the central spot, which became evident soon after the beginning of the examination. Conclusions In light of previous histopathological studies, the central nonfluorescent spot may be interpreted as a masking effect of a pigment clump, whereas the hyper-fluorescent area may represent dye pooling or staining of the subretinal pigment epithelial material.     

Expression of mRNA coding for TNFα, IL-1β and IL-6 by cells infiltrating retinal membranes

Background: Cellular mechanisms of inflammation are thought to be involved in the pathogenesis of proliferative vitreoretinopathy, and cytokines, which are products of cell activation, are known to play an important role in the development and maintainance of inflammatory reactions. It was the aim of this work to investigate the presence of cells expressing cytokine mRNA within retinal membranes. Methods The presence of mRNA coding for the cytokines interleukin 1 (IL-1), interleukin 6 (IL-6) and tumour necrosis factor (TNF) was investigated in 19 epiretinal membranes obtained from eyes undergoing vitrectomy for the treatment of retinal detachment complicated by proliferative vitreoretinopathy. Results Cells expressing mRNA for IL-1 were observed in 7 membranes, cells positive for IL-6 mRNA were seen in 12 membranes, and cells exhibiting mRNA for TNF were present in 9 specimens. Only three membranes contained cells expressing mRNA for all the cytokines investigated. Four membranes possessed positive cells for IL-6 and TNF, two contained cells expressing mRNA for IL-6 and IL-1, and two others exhibited cells expressing mRNA for TNF and IL-1. Five membranes contained IL-6 mRNA-positive cells only, whilst two exhibited cells expressing mRNA for IL-1, or TNF only. Conclusion The present findings indicate that cellular activation may occur during the development of PVR, and suggest that these cytokines may be locally produced by cells infiltrating epiretinal membranes. The presence of IL-1, IL-6 and TNF mRNA-positive cells within retinal membranes provides further evidence of a pathogenic role of these cytokines in proliferative vitreoretinopathy.     

Interpretation of high-pass resolution perimetry with a probability plot

Background: The interpretation of high-pass resolution perimetry (HRP) fields can be difficult. An age-related probability plot was derived from a known data base to determine whether this improved specificity and sensitivity in early glaucoma detection Methods: Forty glaucoma patients with minor field loss and 40 normals of equivalent age and sex underwent HRP. All had previous Humphrey field data available for comparison. The detection of previously confirmed field defects by HRP was examined using different parameters. Results: Using the age-corrected 95% confidence levels gave the best results, with sensitivity of 82.5% (33/40) and specificity of 85% (34/40). Using the contour plot yielded lower sensitivity (67.5%), while subjectively eyeballing the ring printout gave higher sensitivity (90%), but led to poor specificity (72.5%). Conclusion: The use of a probability plot enhances the performance of HRP. A certain proportion of cases may be missed using one criterion alone, but combining the information with other indices can increase the yield.The authors have no proprietary interest in the equipment and technique described herein     

The mydriatic effect of topical glycopyrrolate

Background Glycopyrrolate, an anticholinergic agent that does not cross the blood-brain barrier, has several indications, but its mydriatic effect has never been tested. This study was carried out in order to compare the mydriatic effect of glycopyrrolate 0.5% to that of atropine sulfate 1%. Methods Glycopyrrolate 0.5% and atropine 1.0% were instilled separately in the eyes of albino rabbits. Pupil diameter and intra-ocular pressure were monitored. Results Mydriasis was noted within 5 min of glycopyrrolate instillation, reached near-maximal level at 15 min and persisted for 1 week. Glycopyrrolate 0.5% showed a faster, stronger and more peristent mydriatic effect than atropine 1.0%. Administration of glycopyrrolate 0.5% solution b.i.d. for 1 week did not affect intra-ocular pressure or produce any adverse reaction. Conclusion Glycopyrrolate solution has the potential to deliver an ocular anticholinergic effect without causing associated central anticholinergic hazards.     

The spectrum of eye disease in children with AIDS due to vertically transmitted HIV disease: Clinical findings, virology and recommendations for surveillance

Background: Eye disease in children infected with HIV is uncommon, but there is little information on which children require screening or surveillance and the management of those with retinitis. Methods: We examined 12 children with symptomatic HIV disease (of a cohort of 98 HIV-positive children) using indirect ophthalmoscopy. When retinitis was found it was documented photographically at the time of diagnosis and on follow-up. Results: Four cases of infective retinitis were diagnosed: three with probable cytomegalo-virus retinitis and one with progressive outer retinal necrosis. Conclusion: Detection of reactivation is difficult and we recommend fundus photography under general anaesthesia wherever possible. Children with other end-organ disease, symptomatic eye disease and advanced HIV disease with severe immunosuppression require ophthalmological surveillance.     

Ophthalmological and neuro-ophthalmological involvement in Churg-Strauss syndrome: a case report

Background: It is well known that different types of eye involvement may develop during the course of systemic vasculitides. Methods: We report here a case of Churg-Strauss syndrome (allergic granulomatous angiitis) characterized by the presence of multiple ophthalmological and neuro-ophthalmological lesions, i.e., mononeuritis of the fourth cranial nerve, multifocal choroidal ischaemia, and bilateral ischaemic optic neuropathy. Results: Ischaemic lesions in the posterior ciliary plexus and chorio-retinal circulation, which appeared simultaneously after a phase of disease activity, were documented. Conclusion: The simultaneous occurrence of multiple ocular features in a patient with Churg-Strauss syndrome suggests that regional vasculitis may be the pathological mechanism underlying the multiple ophthalmological lesions in this disorder.     

Precision of ultrasonic estimates of choroidal melanoma regression

Background: Important prognostic information may be gained from knowledge of the volume and, over time, the change in volume of intraocular tumours such as choroidal melanomas. Methods: The precision and time consumption of three different ultrasonographic methods were evaluated. Seven choroidal melanomas were analysed after placement of a ruthenium plaque and again after tumour regression had occurred. Perpendicular ultrasound B-scans were printed and analysed by overlay grid counting or outline tracing of tumour structures to calculate the volume. These two methods, using only two perpendicular scans, were compared with a micro-computer-controlled ultrasonographic three-dimensional rotation scanning system, where each tumour was manually outlined in 20 revolving scan planes. Results: The three-dimensional volume scanning method was the most precise, but also the most demanding in hardware and time consumption. Conclusion: Increased precision and less observer-dependent estimation of shrinkage rate after radiotherapy is available at the cost of sophisticated equipment.     

Microvascular change of the anterior eye segment after tenotomy in the rabbit

Background: The microvascular changes secondary to anterior segment ischemia following tenotomy of the extraocular muscles have not been studied in the rabbit. Methods: Using scanning electron microscopy of methylmethacrylate ocular microvascular luminal castings, the anterior eye segment vasculature after tenotomy was documented and compared to that after occlusion of the bilateral long posterior ciliary arteries and that in the eyes that were not subjected to any surgical intervention. Results: Five days and 1 week after the surgical intervention with tenotomy, microvascular change secondary to the anterior segment ischemia was not apparent, but 2 weeks after the tenotomy subtle evidence of ischemia such as new vessels in the iris was observed. Seven weeks after tenotomy, marked microvascular change was observed where corneal new vessels arose from the superior perilimbal arteries. In contrast, we found prominent microvascular changes 2 weeks after the occlusion of the long posterior ciliary arteries. Conclusions: Tenotomy of the rabbit eye causes microvascular change similar to that in occlusion of the long posterior ciliary arteries. This result suggests that the anterior ciliary artery of the rabbit contributes blood flow to the anterior eye segment and also has a stronger connection with the long posterior ciliary artery than previously reported.     

Integrins in human anterior chamber angle

Background: Integrins, which are composed of an and subunit, are capable of binding to a number of extracellular matrix proteins and, hence, affect cell adhesion and proliferation.Methods: The distribution of the integrin (₁, ₃-₅) and (_1–6 and _v) subunits in human anterior chamber angle was studied in eyes from subjects aged 9 months to 81 years using the indirect immunofluorescence technique.Results: Immunoreaction for the ₁ subunit was found throughout the trabecular meshwork (TM), in the cribriform layer, and in the endothelial lining of Schlemm's canal (SC). Labelling for the ₃ subunit was found in the TM and the cribriform layer only. In infant eyes the ₅ subunit was present in all three areas with the highest concentration in the cribriform layer, whereas no reaction was observed in adult eyes. The ₆ subunit was localized to the endothelium of SC only. Immunoreaction for the _v subunit was present in the TM and the cribriform layer of infants and young adults.Conclusion: The present results suggest the presence of several integrin heterodimers, acting as potential receptors for laminin, collagen, fibronectin, and vitronectin, in the anterior chamber angle.     

Magnetic resonance imaging of cyclodialysis clefts

Background: Our purpose was to determine whether cyclodialysis clefts can be imaged with magnetic resonance imaging (MRI). Methods: Surgical cyclodialysis clefts extending approximately 3 clock hours were created in four New Zealand white rabbits. Eyes were scanned with an ocular MRI coil. Images obtained after intravenous gadolinium, topical godalinium, and gadolinium injected into the cleft were compared to images obtained without contrast. Two human eyes were also scanned for cyclodialysis clefts with MRI. Results: Direct injection of gadolinium into the suprachoroid space yielded definitive localization and delineation of the cyclodialysis cleft. Cyclodialysis clefts could also be imaged following enhancement with topical or intravenous gadolinium. Without contrast medium, the clefts could not be clearly identified in rabbits. In a patient with hypotony and choroidal effusion following cataract surgery, a cyclodialysis cleft and enhancement of the suprachoroidal space were found with intravenous administration of gadolinium. MRI from a patient with a trabeculo-suprachoroidal shunt also demonstrated gadolinium enhancement of the suprachoroidal space. Conclusion: Cyclodialysis clefts can be imaged using gadolinium-enhanced MRI in rabbits and humans.The authors have no proprietary interest in the companies or products mentioned in this articlePresented in part at the Annual Meeting of the Association for Research in Vision and Ophthalmology, Sarasota, Fla. 15 May 1995     

Effects of norfloxacin on the retina in rabbits

Background: Fluoroquinolones have a strong affinity with melanin, and their ocular effects have been reevaluated. Norfloxacin, one of the fluoroquinolones, has broad-spectrum activity against aerobic gram-positive and gram-negative bacteria. We examined the retinal toxicity and intraocular pharmacokinetics of intravitreal norfloxacin in rabbits. Methods: Twenty-three albino and 23 pigmented rabbits were divided into three groups to evaluate retinal toxicity and two groups to investigate the intraocular pharmacokinetics. Each of these five groups was further divided into two subgroups (albino rabbits and pigmented rabbits). Results: With 500 Etg norfloxacin, the oscillatory potential of the electroretinogram was transiently and selectively deteriorated in albino and pigmented rabbits, whereas the electroretinogram remained unchanged with 50 g in pigmented rabbits. No changes were observed in the visual evoked potential or on histology of the retina 7 days after an intravitreal injection of 50 or 500 ltg norfloxacin. The electroretinogram and the retinal histology became abnormal 7 days after four intravitreal injections of 500 g norfloxacin at 7-day intervals. As regards the intraocular pharmacokinetics after an intravitreal injection, the norfloxacin concentration in the chorioretina was as high as that in the vitreous 3 h after injection and was much higher than that in the vitreous 7 days after injection. Similar results were obtained after multiple injections. Conclusion: These results indicate a high concentration of norfloxacin in the melanin-containing ocular tissues.     

Blood-retina barrier in acute retinal branch vein occlusion

Background: Extensive clinical studies on retinal branch vein occlusion have not yet been able to clarify its pathogenesis. A study designed to look at the associated blood-retina barrier changes may contribute to a better understanding of the different forms of evolution of this pathology. Methods: A prospective study was done in seven patients with recent large temporal branch vein occlusion. Vitreous fluorophotometry, fluorescein angiography and retinal colour photography were performed within the 1st week after the onset of symptoms, 1 week later, and at 12 and 24 weeks. Results: A more marked blood-retina barrier breakdown was found at 1, 2, 12 and 24 weeks in the eyes that later developed extensive capillary non-perfusion. Conclusions: Our results suggest that the breakdown of the blood-retina barrier may play an important role in the subsequent development of retinal nonperfusion in eyes with large branch vein occlusion. We postulate that the eyes that will present later extensive capillary nonperfusion develop, from the initial stages of the disease, a progressive ischaemic capillaropathy characterized by blood-retina barrier breakdown. Retinal pigment epithelium degeneration and arterial lumen narrowing, secondary to the vein obstruction, may help to increase and perpetuate the blood-retina barrier breakdown during the first 6 months after the occlusion.     

Angiogenesis in early choroidal neovascularization secondary to age-related macular degeneration

Background: The morphological features of angiogenesis in early choroidal neovascularization secondary to age-related macular degeneration are yet to be fully described. Methods: Six eyes from five patients which on clinical and histological examination showed advanced age-related macular degeneration and early choroidal neovascularization have been studied by transmission electron microscopy. Results: Pre-existing choroidal capillaries and venules showed changes which included endothelial cell budding, pericyte enlargement, endothelial cell sprout formation and the development of intrachoroidal new vessels. In one case, an endothelial cell sprout continuous with an intrachoroidal vessel penetrated Bruch's membrane. Examination of early subretinal pigment epithelial new vessels showed them to spread between the inner layers of Bruch's membrane within the space usually occupied by the basal linear deposit and drusen. New vessel formation took place in blind pouches at the margins of new vessel networks, either in the absence of pericytes or in the presence of mainly myofibroblast-like pericytes. Conclusion: This ultrastructural study describes two phases of new vessel growth associated with the onset of choroidal neovascularization secondary to age-related macular degeneration. The initial intrachoroidal phase appears to be a low-turnover form of neovascularization which may lead to new vessels penetrating Bruch's membrane. Extensive subretinal pigment epithelial neovascularization, on the other hand, results from a high-turnover phase of neovascularization characterized by extensive endothelial cell proliferation and migration. Pericyte phenotypic changes associated with these different phases of neovascularization appear to relate to the dynamics of angiogenesis taking place in each process.     

Hypoxia precedes the development of experimental preretinal neovascularization

Background: Although the mechanism of preretinal neovascular growth in the cell-injected rabbit eye model is not known, it has been proposed that the initial vasodilation and eventual development of neovascularization may be attributable to inflammatory mediators. However, an alternative explanation involving hypoxia has not been considered. The purpose of this study was to measure preretinal oxygen tension prior to the development of preretinal neovascularization in the cell-injected rabbit eye. Methods: In the rabbit, intravitreous injections of 250 000 homologous dermal fibroblasts were performed on one eye; the fellow (control) eye was injected with vehicle. Preretinal oxygen tension over the myelin wing was measured using¹⁹F-NMR spectroscopy of a 30-l droplet of perfluorocarbon previously injected into the preretinal vitreous. Results: Compared to control eyes, fibroblast-injected eyes showed a 1.7-fold decrease in preretinal oxygen tension from the first time studied (1 day after cell injection) through the development of visible neovascularization. Hypoxia occurred without coexisting ophthalmoscopic evidence of vascular occlusion or, on days I and 3 after cell injection, retinal detachment. Conclusion: This result demonstrates for the first time that preretinal hypoxia precedes the development of reretinal neovascularization in the fibroblast-injected rabbit eye.     

Mediators of the ocular inflammatory response to interleukin-1β plus tumor necrosis factor-α

Background: Intravitreal injection of marginally inflammatory doses of interleukin-1 and tumor necrosis factor- (IL-1 /TNF) has been shown to produce intraocular inflammation distinctly different from that induced by higher intravitreal doses of either IL-1 or TNF. Since cyclooxygenase inhibitors and platelet-activating factor (PAF)-receptor antagonists can reduce IL-1- or TNF-induced uveitis, the present investigation was undertaken to determine whether cyclooxygenase metabolites of arachidonic acid and PAF are important mediators of IL-1/TNF-induced uveitis. Methods: The cyclooxygenase inhibitor indomethacin and two structurally dissimilar PAF-receptor antagonists, SRI 63-441 and WEB 2086, were used to investigate the importance of cyclooxygenase metabolites and PAF in IL-1/TNF-induced uveitis. Results: Based upon the effectiveness of indomethacin, the anterior uveitis induced by IL-1/TNF could be divided into two phases; a primary phase dependent upon generation of cyclooxygenase metabolites (the first 24 h) and a secondary phase largely independent of cyclooxygenase metabolite production (24–48 h). Posterior uveitis was also apparent at 48 h and was reduced by indomethacin. SRI 63-441 reduced the anterior uveitis at 24 h and to a lesser extent at 48 h; it also reduced the posterior uveitis at 48 h. However, although WEB 2086 was as effective as SRI 63-441 in reducing PAF-induced platelet aggregation, ex vivo, it did not significantly reduce IL-1/TNF-induced uveitis. Conclusions: Although the findings do not support an important role for PAF in TNFa/IL-1-induced uveitis, it cannot be ruled out that more intensive treatment with a specific and long-acting PAF-receptor antagonist might yield more positive results.