The effect of nasolacrimal occlusion on drug-induced mydriasis

Background: Nasolacrimal occlusion has been shown to improve the efficacy of some topically applied ocular drugs. The aim of this study was to investigate the effect of nasolacrimal occlusion on tropicamide-induced mydriasis. Methods: We compared pupillary dilatation by 0.125% tropicamide with and without nasolacrimal occlusion in 40 healthy volunteers. Results: Analysis of variance with repeated measures failed to show any advantage due to nasolacrimal occlusion in drug-induced mydriasis. Conclusion: Nasolacrimal occlusion did not increase the mydriasis obtained with 0.125% tropicamide.     

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.     

Bilaterality of idiopathic macular holes

Background: There has been wide variation in estimates of the incidence of bilateral idiopathic macular holes in the literature. This report of a large series of patients with macular holes provides further information regarding incidence of bilaterality, interval between onset in the first and the second eye, and visual outcome. Methods: A retrospective chart review was done of 550 patients with idiopathic macular holes examined at the Bascom Palmer Eye Institute between 1968 and 1994. The incidence of bilaterality was estimated from 365 patients in whom the fellow eye was normal at the initial examination. The rate of onset in the fellow eye was evaluated by survival analysis. Mean follow-up was 31 months (median 17 months). Results: Patients with incomplete macular holes (stage 1, aborted stage 1, lamellar) or full-thickness holes had a 19% incidence of bilaterality at 48 months follow-up. In the subset of 32 patients with full-thickness macular holes in the first eye, 13% developed full-thickness holes in the fellow eye within 48 months. The median interval between the onset in the first and in the second eye was 17.5 months. Visual acuity was excellent and stable in eyes with aborted stage 1 and lamellar holes. The visual acuity in the first eye with full-thickness macular hole decreased to 20/200 or worse in 79% of cases within 36 months' follow-up. Conclusions: The incidence of bilaterality and poor visual function in the majority of full-thickness idiopathic macular holes by 3 years' duration should be considered when advising patients and planning management.     

The effect of chemical stability and purification of perfluorocarbon liquids in experimental extended-term vitreous substitution

Background: To determine the importance of chemical stability and purification of perfluorocarbon liquids (PFCLs) in experimental retinal tolerance, we tested four different substances as long-term vitreous tamponade: purified and nonpurified perfluorodecalin (PFD) and perfluoro-octylbromide (PFOB) Method: After mechanical vitrectomy we replaced the vitreous of 65 rabbit eyes. Five groups were formed; four of them received the four PFCLs, while one served as control and received Ringer solution. The eyes were observed clinically every week and examined histologically after 1, 2, 4 and 8 weeks Results: After 1 week we observed foam cells and intraretinal macrophages in all eyes with PFCLs. Purified PFD caused retinal lesions in the photoreceptor, ganglion cell and outer nuclear layers after only 2 weeks in the lower part of the eyes. In eyes filled with purified PFOB we observed more pronounced damage of the same nature. Unpurified substances caused severe inflammation and retinal detachment Conclusion: Our study demonstrates that purification and chemical stability are important factors in retinal tolerance of PFCLs for vitreous replacement. Although purified PFD was tolerated by the rabbit eyes for 1 week, we cannot recommend this substance for short-term clinical use as a vitreous substitute.     

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.     

Aqueous flare in eyes with senile disciform macular degeneration: correlation with clinical stage and area of neovascular membrane

Background: The aim of the present study was to investigate the aqueous flare in eyes with senile disciform macular degeneration (SDMD), divided into different clinical stages, and the correlation between the aqueous flare and the area of the neovascular membrane. Methods: Eighty-six eyes of 44 patients with SDMD were examined using a laser flare meter. The area of the neovascular membrane was measured by means of a digitizer in images obtained using indocyanine green videoangiography. Results: The mean value of the aqueous flare was 5.91±2.51 (photon count/ms) in 7 predisposing stage eyes, 5.68 ± 1.64 in 15 initial stage eyes, 9.09 ± 7.65 in 24 advanced form eyes, 5.40 ± 1.42 in 11 disciform scar eyes, and 5.36 ± 1.72 in 29 fellow eyes. The aqueous flare value was significantly (P<0.01) higher in eyes with the advanced form of SDMD than in the fellow eyes. There were no significant differences in aqueous flare values between eyes with predisposing stage, initial stage, and disciform scar and fellow eyes. The aqueous flare value increased significantly with increasing area of neovascular membrane (R\s=0.68, P<0.01). Conclusion: The present results suggest that the aqueous flare increases with increasing neovascular membrane area in eyes with SDMD, and decreases with scarization of the neovascular membrane.     

Primary vitrectomy without scleral buckling for rhegmatogenous retinal detachment

Background: Pars planta vitrectomy has evolved as an alternative method in the treatment of more complicated rhegmatogenous retinal detachments. We report a series of patients who underwent primary vitrectomy with gas tamponade without the use of additional scleral buckling. Methods: A retrospective study of 53 patients with a follow-up of 6–45 months (mean 17.8 months) was carried out. Preoperative findings included unusual, multiple or large breaks, vitreous haemorrhage, proliferative vitreoretinopathy and bullous retinal detachment. Preoperative visual acuity was between light perception and 1.0, with 30% (16/53) of patients with 0.4 or better. Results: Retinal reattachment was achieved in 64% of cases (34/53) with one and in 92% (49/53) with one or more operations. Final visual acuity was between light perception and 1.0, with 41% (22/53) of patients with 0.4 or better. Cataract formation occurred in 86% (37/43) of all patients with a clear lens preoperatively. Macular pucker was noted in 11 % (6/53) and postoperative proliferative vitreoretinopathy causing redetachment in 6% (3/53). Conclusion: With primary vitrectomy, a high final anatomical success rate with few intraoperative complications can be achieved in more complicated forms of rhegmatogenous retinal detachment. The major drawback of the procedure is the high incidence of post-operative cataract formation.     

Pressure sore in a patient who underwent repair of a retinal tear with gas injection

Purpose: To demonstrate a pressure sore following strict head positioning in a patient who underwent encircling band, vitrectomy and gas injection. Methods: A male patient was admitted to the hospital with a large posterior horseshoe tear in the inferior temporal retina with severe vitreous traction and retinal detachment. Encircling band, vitrectomy cryotherapy and gas injection was performed. After surgery the patient was instructed to sit in a facedown position. Results: A pressure sore resulted from prolonged immobility of the right elbow due to face-down positioning following encircling band, vitrectomy and gas injection. Conclusion: A patient injection. Conclusion: A patient may rarely have compulsive personality traits that result in extreme compliance to the physician's recommendations; therefore, general instructions given for head positioning should include permission for a change in position when required, at least for brief periods of time.     

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.     

Autologous platelet concentrate for the treatment of full-thickness macular holes

Background: To improve the anatomic success rate in the surgery of full-thickness macular holes, we tested, in a prospective pilot study, the effects of autologous platelet concentrate deposited on the macula at the end of surgery. Methods: Two consecutive groups of patients were compared. Twenty eyes (group 1, mean symptom duration 11 months) were operated on with injection of an autologous platelet concentrate on the macula after fluid-gas exchange. Another 20 eyes (group 2, mean symptom duration 11 months) were subsequently operated on without autologous platelet concentrate. For all stage 3 holes, posterior hyaloid was detached en bloc at the level of the optic disc. The patient was left supine for 24 h after surgery, and then remained face down for 10 days. Results: In group 1, 19 cases were an anatomic success, i.e. there was flattening of the retina surrounding the hole and reattachment of the edge of the hole to the retinal pigment epithelium; in 9 cases the hole was even undetectable. Final visual acuity was 0.5 or more in 9 eyes, and 0.4 or more in 14. Visual acuity improved by two lines or more in 17 of the 19 successfully operated eyes. In group 2, only 13 cases were an anatomic success. The functional results for the successfully operated eyes were identical to those of group 1. Conclusion: These results strongly suggested that autologous platelet concentrate could significantly improve the success rate in macular hole surgery and led us to begin a comparative, prospective, randomized trial.Paper presented at the 17th meeting of the Club Jules Gonin, Versailles, September 1994     

Characteristics of endogenous uveitis in Hokkaido, Japan

Background: Etiological characteristics of endogenous uveitis vary around the world. There are few epidemiological reports on the etiology of uveitis from areas within Asia. We set out to examine the statistical data on uveitis in Japan. Methods: We reviewed all the records of patients with endogenous uveitis who visited the Uveitis Survey Clinic of Hokkaido University Hospital in 1981 and 1994 and extended the survey to include new patients with uveitis seen over the past 3 years. Results: Behçet's disease, sarcoidosis and Vogt-Koyanagi-Harada disease were the three most frequently diagnosed diseases in patients with endogenous uveitis in both 1981 and 1994. The proportion of patients with unclassified disease entities decreased (from 38% to 30%) during the 13-year period from 1981 to 1994 as a result of the new disease categories established during this interval. Notable additions included human T-lymphotropic virus type I-associated uveitis and tubulointerstitial nephritis and uveitis syndrome. Sarcoidosis is now the most frequent cause of endogenous uveitis in our clinic. Conclusion: Not only does the etiological basis of uveitis vary with ethnicity, but advances in clinical and basic research have changed the approach to the diagnosis of uveitis, altering the etiological profile over time.     

Plasminogen activation in epiretinal membranes

Background: Formation of epiretinal membranes occurs in proliferative vitreoretinopathy, macular pucker and after penetrating trauma. Epiretinal membrane formation includes cell migration and proliferation, extracellular matrix formation and tissue contraction. Generally in scar tissue formation, the production of new extracellular matrix occurs concomitantly with its proteolytic degradation, resulting in continuous tissue remodelling. The plasminogen activator-mediated proteolytic cascade is an important mechanism for pericellular degradation of the extracellular matrix. Therefore we wanted to study the presence of the plasminogen activator-mediated proteolytic cascade in epiretinal membranes. Methods: Specimens of 18 epiretinal and 3 subretinal membranes were obtained during vitreous surgery for retinal detachment with proliferative vitreoretinopathy or macular pucker. Plasminogen activators and plasmin were characterized in frozen sections of epiretinal membranes by in situ zymography and in membrane lysates by zymography. Indirect immunofluorescence staining was performed to localize urokinase in epiretinal membranes. Results: Urokinase was present in 17/21 and tissue-type plasminogen activator in 12/21 of the membranes studied. Active plasmin was not detected in the frozen sections of epiretinal membranes. Immunofluorescence staining localized urokinase predominantly in the areas invaded by macrophages and cells of retinal pigment epithelial origin. Conclusion: Our results demonstrate the presence of proteolytic activity in periretinal scar tissue. Urokinase was more consistently present, but smaller amounts of tissue-type plasminogen activator were also found in the specimens. These results indicate that continuous tissue remodelling with simultaneous extracellular matrix production and breakdown regulates the growth of epiretinal membranes.     

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.     

Increased lipid peroxide level and myeloperoxidase activity in the vitreous of patients suffering from proliferative vitreoretinopathy

Background: Retinal pigment epithelium cells and activated phagocytes are believed to be involved in the pathogenesis of proliferative vitreoretinopathy (PVR). Both cell types are capable of producing oxygen free radicals and other molecules with a high oxidative potential which can lead to a propagation of oxidative damage. It was the aim of this study to investigate whether products of oxidative reactions are detectable in the vitreous body of patients suffering from PVR. Methods: In vitreous aspirates of patients vitrectomized because of PVR (n = 27), macular pucker (n = 9), or other reasons (controls, n = 31), the following parameters were determined: lipid peroxides (LPO), determined as malondialdehyde-like substances (MDA) and as thiobarbituric acid-reactive substances (TBARS), and myeloperoxidase activity (MPO). Results: Compared with the controls, both LPO levels and MPO activities were significantly elevated in the vitreous of patients suffering from PVR. Vitreous of patients with macular pucker did not reveal any significant differences from controls in the parameters analyzed. Conclusion: Our results suggest that both oxygen free radicals and inflammation-related reactions participate in the process of PVR. Oxidative tissue damage is obviously not involved in the pathogenesis of macular pucker.This study was presented in part at the first annual meeting of ECORA, 4–6 October, 1993 in Bonn     

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 use of tissue plasminogen activator in post-traumatic total hyphaema

Background: We wanted to evaluate whether intracameral injection of tissue plasminogen activator (tPA) is useful in managing traumatic hyphaema. Methods: Two eyes with total hyphaema after a severe penetrating injury were treated with a single intracameral injection of 25 g of tPA 5 and 14 days after the injury, respectively. Results: Most of the blood coagulum dissolved within 24 h, and in one of the two eyes the intraocular pressure decreased from 45 to 8 mmHg. The other eye was hypotonic. No re-bleeding or complications related to the use of tPA were noticed. Conclusion: The results in these two cases suggest that tPA is a useful adjunct in managing total hyphaema.     

Surgical risk factors for severe postoperative proliferative vitreoretinopathy (PVR) in retinal detachment with grade B PVR

Background: Previous studies have shown that grade B proliferative vitreoretinopathy (PVR) is a considerable risk factor for the development of severe postoperative PVR. We conducted a prospective study to elucidate which surgical procedures used in retinal detachment management may stimulate the PVR process in such eyes. Materials and methods: The study included 156 eyes of 152 consecutive patients with rhegmatogenous retinal detachment complicated by grade B PVR referred before any failed surgery and operated on between 1983 and 1993. The parameters evaluated by multivariate statistical analysis included the cumulative circumferential extent of the retinal tears, the extent of the scleral buckle, gas injection, vitrectomy, the method used for retinopexy, and the time of surgical management during the period of the study. Results: The incidence of severe postoperative PVR was 25.8% in eyes managed with cryotreatment versus 2.2% in eyes managed with argon laser photocoagulation (P=0.001). The rate of severe postoperative PVR was not influenced by the other surgical variables. Conclusion: We conclude that cryotherapy may be a risk factor for the development of severe postoperative PVR in retinal detachments associated with grade B PVR.     

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.     

Indocyanine green angiography and age-related serous pigment epithelial detachment

Background: Fundus fluorescein angiography has shown that pigment epithelial detachment in age-related macular degeneration is often associated with choroidal neovascularisation (CNV). Indocyanine green angiography (ICG-A) provides a better visualisation of choroidal circulation and of CNV than fluorescein angiography (FA). Methods: We studied the ICG angiograms of 58 eyes presenting age-related pigment epithelial detachment, either with signs of occult CNV (48 eyes) or without signs of CNV (10 eyes) on FA. In selected cases the neovascular complex defined on the ICG angiogram was photocoagulated. Results: ICGA-revealed hyperfluorescence interpreted as CNV in 46 of 48 eyes with fluorescein angiographic signs of occult choroidal neovascularisation. The neovascular complex seen on the ICG angiogram was well delineated in 29 eyes and ill defined in 17 eyes. ICG-A revealed CNV in 2 of 10 eyes without signs of CNV on FA. In these two cases the neovascular complex was ill defined. Photocoagulation in selected cases resulted in stabilisation or even improvement of visual acuity and flattening of the pigment epithelial detachment in 9 of 18 cases. Conclusion: ICG-A may offer a better definition of the neovascular complex associated with pigment epithelial detachment in age-related macular disease and be helpful in guiding laser treatment. In some cases FA still outlines more clearly the lesions to be treated. FA and ICG-A should thus be used concurrently to determine treatment strategy.     

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