Retinal toxicity of intravitreal tenecteplase in the rabbit.

AIM: To investigate the retinal toxicity of intravitreal injection of a novel fibrinolytic tenecteplase in rabbit eyes. METHODS: Tenecteplase (25-350 micro g in 0.1 ml BSS) was injected into the vitreous cavity of normal rabbit eyes. Control (fellow) eyes received 0.1 ml of BSS. One day, 1 week, and 2 months post-injection, the eyes were examined by slit lamp biomicroscopy, indirect ophthalmoscopy, and electroretinography, and then harvested for histopathological examination. RESULTS: No evidence of retinal toxicity was seen with tenecteplase doses up to and including 50 micro g. At a dose of 150 micro g ophthalmoscopy was normal, but histology showed mild retinal damage in the inner nuclear layer and electroretinography showed a temporary reduction in B-wave amplitude. At doses of 200 micro g and above, there was evidence of retinal toxicity on electroretinography, ophthalmoscopy, and histology. Ophthalmoscopic findings included vitreal fibrosis, retinal necrosis and tractional retinal detachment and light microscopy revealed necrosis of retinal pigment epithelium and other retinal layers. Damage was centred around the injection site but was more widespread with the higher doses. CONCLUSION: A dose of 50 micro g tenecteplase appears safe for intravitreal injection in the rabbit. Tenecteplase could have potential applications in the treatment of submacular haemorrhage and retinal vein occlusion.

Bowel carcinoma metastatic to the retina.

The case is presented of metastatic carcinoma to the retina in a 63-year-old woman with known disseminated large bowel carcinoma. The clinical appearance and angiographic features are discussed.

Telemedicine screening of diabetic retinopathy using a hand-held fundus camera.

The objective was to evaluate digital images of the retina from a handheld fundus camera (Nidek NM-100) for suitability in telemedicine screening of diabetic retinopathy. A handheld fundus camera (Nidek) and a standard fundus camera (Zeiss) were used to photograph 49 eyes from 25 consecutive patients attending our diabetic clinic. One patient had cataracts, making it impossible to get a quality image of one of the eyes (retina). The Nidek images were digitized, compressed, and stored in a Fujix DF-10M digitizer supplied with the camera. The digital images and the photographs were presented separately in a random order to three ophthalmologists. The quality of the images was ranked as good, acceptable or unacceptable for diabetic retinopathy diagnosis. The images were also evaluated for the presence of microaneurysms, blot hemorrhages, exudates, fibrous tissue, previous photocoagulation, and new vessel formation. kappa Values were computed for agreement between the photographs and digital images. Overall agreement between the photographs and digital images was poor (kappa < 0.30). On average, only 24% of the digital images were graded as being good quality and 56% as having an acceptable quality. However, 93% of the photographs were graded as good-quality images for diagnosis. The results indicate that the digital images from the handheld fundus camera may not be suitable for diagnosis of diabetic retinopathy. The images shown on the liquid crystal display (LCD) screen of the camera were of good quality. However, the images produced by the digitizer (Fujix DF-10M) attached to the camera were not as good as the images shown on the LCD screen. A better digitizing system may produce better quality images from the Nidek camera.

Laser-induced chorioretinal venous anastomosis for nonischemic central retinal vein occlusion: evaluation of the complications and their risk factors.

PURPOSE: To evaluate the complications of laser-induced chorioretinal venous anastomosis in nonischemic central retinal vein occlusion (CRVO) and to identify the associated risks. METHODS: A retrospective consecutive series of 91 eyes (91 patients) with nonischemic CRVO with a mean +/- SD duration of 15.0 +/- 15.2 weeks (range, 3 to 72 weeks )and corrected visual acuity reduced to 20/100 or less because of perfused macular edema were reviewed. All eyes had one or more anastomotic attempts using argon laser (combined with Nd-YAG laser in 46 eyes) and a minimum of 12 months of follow-up. RESULTS: Successful chorioretinal venous anastomoses were created in 49 eyes (54%). Eighteen eyes (20%) had neovascular complications. These consisted of intravitreal, intraretinal, and subretinal neovascular membranes and were significantly associated with retinal ischemia (P < .001). There was avascular fibrous tissue proliferation at the anastomotic site in eight eyes (9%), and it was not associated with retinal ischemia (P = .727). No eye developed further capillary nonperfusion once an anastomosis became functional. A chorioretinal venous anastomosis was associated with improved vision (P < .001); 84% of eyes had an average +/- SD improvement of 4.3 +/- 3.8 lines (range, 2 to 20 lines), with the remaining 16% having no improvement or reduced vision. CONCLUSION: The major vision-threatening complication of laser-induced chorioretinal venous anastomosis for nonischemic CRVO is neovascular membranes occurring at the anastomotic site; these are associated with retinal ischemia. Prompt laser photocoagulation to areas of retinal ischemia that develop after the anastomotic attempt has been made may reduce the risk and severity of this complication.

Non-mydriatic fundus photography: a viable alternative to fundoscopy for identification of diabetic retinopathy in an Aboriginal population in rural Western Australia?

PURPOSE: To evaluate the Canon CR5-45NM non-mydriatic fundus camera (Canon, Kanagawa, Japan) for identifying retinopathy and the need for laser treatment in a population of Aboriginal patients with diabetes mellitus in rural Western Australia. METHODS: Diabetic Aboriginal patients were photographed through undilated pupils using a Canon CR5-45NM non-mydriatic fundus camera, after which ophthalmoscopy was performed using indirect ophthalmoscopy through dilated pupils. The examining ophthalmologist recorded the presence of retinopathy and the need for laser treatment. A proportion of patients were rephotographed through dilated pupils. Photographs were reviewed by a second ophthalmologist who evaluated the quality of the image, the presence of retinopathy and the need for laser treatment. Results of fundus photographs and ophthalmoscopy were compared. RESULTS: Three hundred and twenty-eight eyes in 164 Aboriginal patients were examined. The mean patient age was 48.2 years (range 16-81 years) and the mean duration of diabetes was 7.5 years (range 1-35 years). Seventy-four eyes (22.6%) were diagnosed with retinopathy using combined examination techniques, 44 (59.5%) of which were identified by ophthalmoscopy and 55 (74.3%) by photography. Thirty-five eyes were deemed to need treatment, 18 (51.4%) of which were identified by ophthalmoscopy and 30 (85.7%) by photography. Kappa coefficient measurement for agreement for presence of retinopathy and need for referral was 0.41 and 0.53, respectively. Photograph quality was significantly improved following pupil dilation. CONCLUSIONS: The Canon CR5-45NM non-mydriatic fundus camera was relatively good at identifying diabetic retinopathy and could usefully be applied within a screening programme for treatable disease within this population.

Chorioretinal venous anastomoses: effect of different laser methods and energy in human eyes without vein occlusion.

BACKGROUND: This study was performed to determine the laser energy required to rupture both Bruch's membrane and retinal veins reliably in order to create a venous chorioretinal anastomosis. METHODS: A histological examination was conducted of argon green and YAG laser applications to the retina made prior to enucleation in eight eyes with large intraocular melanomas. RESULTS: Argon laser application of 50 microns in size and 0.1 s duration to intervascular areas of the retina will reliably rupture Bruch's membrane at a power level of at least 1.5 W. If the argon laser spot is placed overlying a retinal vein, a power level of up to 2.5-3.0 W will rupture Bruch's membrane in 60%, with only 34% of the retinal veins showing evidence of rupture. The YAG laser with power levels of 3-4 mJ will reliably rupture the retinal vein in cases where it has not previously been ruptured by the argon laser. CONCLUSION: When attempting to create a chorioretinal venous anastomosis in an eye with a non-ischaemic central retinal vein occlusion, Bruch's membrane should be ruptured first by placing the argon laser application at the side of the retinal vein before an attempt to rupture the retinal vein itself is made in case haemorrhage from the ruptured vein obscures the view. A power level of at least 2.5 W should be used. If the argon laser is unsuccessful in rupturing the retinal vein, a YAG laser (3-4 mJ) is effective.

The distribution of angioarchitectural changes within the vicinity of the arteriovenous crossing in branch retinal vein occlusion.

OBJECTIVE: Branch retinal vein occlusions (BRVOs) are known to occur most commonly in the vicinity of arteriovenous (A/V) crossings. The authors aimed to identify types of venous wall abnormalities in BRVO and document their position in relation to the A/V crossing. DESIGN: A retrospective review of the color photographs and fluorescein angiograms from the most recent 110 patients with first- or second-order BRVO was performed. MAIN OUTCOME MEASURES: The films were examined for the presence of angioarchitectural changes of specified type within one-quarter disk diameter of the A/V crossing involved in the BRVO. The specific changes noted were fluorescein leakage, presumed thrombi, and flow abnormalities, which were recorded along with their position in relation to the A/V crossing. RESULTS: Of the 110 patients diagnosed with BRVO, 59 had photography of satisfactory quality. Forty-one (70%) of these 59 patients had venous lesions, of which significantly more (chi-square -5.74, P < 0.02) were downstream (56%) than upstream (12%) from the A/V crossing. Thirty-two percent were upstream and downstream. Of the hemodynamic changes seen, 49% had late venous phase leakage of fluorescein, 85% had abnormal flow, and 7% had presumed thrombi. All thrombi seen were downstream. CONCLUSIONS: Venous lesions in the vicinity of the A/V crossing commonly are seen in BRVO, most of which occur downstream. This suggests that the venous narrowing at the crossing may induce downstream hemodynamic changes predisposing to endothelial damage and thrombus generation.

Retinal detachment caused by retinal dialysis.

PURPOSE: To determine the characteristics of patients developing retinal detachment secondary to retinal dialysis in Western Australia and to confirm the clinical impression that these patients had a low rate of proliferative vitreoretinopathy (PVR). METHODS: A retrospective analysis of the records of 1601 consecutive patients with rhegmatogenous retinal detachment identified 71 patients in whom the retinal detachment was caused by a retinal dialysis. RESULTS: The majority of these patients were young adults (mean age of 30 years) and the male to female ratio was 1.3:1. Seventy per cent of patients provided a history of significant trauma to the affected eye. Sporting injuries, assault, and motor vehicle injuries together accounted for 72% of identifiable trauma. Examination revealed a dialysis of the inferotemporal quadrant in 75% of cases and despite obvious signs of chronicity of the associated retinal detachment (such as intraretinal macrocysts and demarcation lines) in approximately one-third of the eyes, only 5.6% developed grade CI PVR either pre- or postoperatively. CONCLUSION: The present study supports the view that it is the low rate of PVR that explains the good prognosis and high surgical success rate for retinal detachments caused by retinal dialysis. It is postulated that a major reason for the low rate of PVR is that the vitreous base attachment to the posterior margin of a retinal dialysis acts as a significant barrier to the migration of potentially proliferative retinal pigment epithelial cells. This may lead to containment of the responsible proliferative cells within the loculated subretinal space.

Suprachoroidal effusion following argon laser trabeculoplasty.

PURPOSE: This is first report of suprachoroidal effusion occurring subsequent to argon laser trabeculoplasty (ALT). METHODS: Review of the records of the patients in question. RESULTS: A 77-year-old woman with bilateral pseudophakia and primary open-angle glaucoma was treated with ALT when her visual fields deteriorated despite topical timolol therapy. Although ALT was initially performed without complication in one eye, treatment of the other eye led to a choroidal detachment. This was associated with temporary reduction in visual acuity, shallowing of the anterior chamber and hypotony. CONCLUSION: Suprachoroidal effusion appears to be another complication of ALT. In the reported case, this application and its effects were temporary and resolved with conservative management.

Poly(1-vinyl-2-pyrrolidinone) hydrogels as vitreous substitutes: histopathological evaluation in the animal eye.

A homopolymer of 1-vinyl-2 pyrrolidinone and its copolymer with 2-hydroxyethyl methacrylate, both cross-linked with divinyl glycol, were produced as possible substitutes for the vitreous body of the eye. The hydrated polymers behaved like viscoelastic gels, displaying excellent physical and optical properties. The sterile gels (0.7-1.5 ml) were injected into the vitreous cavity of rabbits, which previously underwent gas-mediated vitrectomy. Clinically, the eyes were quiet, with the exception of transient opacities in the vitreous. After 4 weeks, the operated eyes were enucleated and subjected to histopathological analysis using light and transmission electron microscopy. The common feature in all sections was the invasion of inflammatory cells. Vacuoles containing granular material, assumed to be polymer, were seen in the intercellular spaces of the neural retina, in the retinal pigment epithelium cells, and in macrophages. These findings indicated the fragmentation and phagocytosis of synthetic gels. It appeared that the biodegradation of the internalized polymers did not proceed further, however, the fate of polymers and their usefulness as vitreous substitutes should be investigated through long-term experiments.

Laser-induced chorioretinal venous anastomosis for treatment of nonischemic central retinal vein occlusion.

OBJECTIVES: To determine whether a chorioretinal venous anastomosis could be created in humans and to evaluate the influence this has on patients with nonischemic central retinal vein occlusions in whom progressive visual loss developed. DESIGN: Retrospective study. PATIENTS: A total of 24 patients with nonischemic central retinal vein occlusions and progressive visual loss. INTERVENTION: An attempt was made to create a chorioretinal venous anastomosis using laser photocoagulation to enable obstructed venous blood to enter the choroid, thus bypassing the site of occlusion. MAIN OUTCOME MEASURES: Visual acuity, funduscopic appearance, and rapid sequence fluorescein angiograms. RESULTS: A successful chorioretinal venous anastomosis was created in eight cases (33%), with improvement in visual acuity and resolution of the funduscopic appearance of venous occlusion in all eight cases. Of the 16 patients (67%) in whom an anastomosis was not successfully created, the ischemic form of central retinal vein occlusion developed in five (31%), and eight (50%) were left with various degrees of macular damage and reduced visual acuity. CONCLUSIONS: Peripheral chorioretinal venous anastomoses can be created in a nonischemic central retinal vein occlusion and appear to be well tolerated. This technique may have some value in the treatment of patients with this condition; however, to address this fully, a properly constructed randomized prospective clinical trial will need to be performed.

Initial clinical experience with tissue plasminogen activator (tPA) assisted removal of submacular haemorrhage.

Tissue plasminogen activator (tPA) (250 micrograms/ml) was used to facilitate removal of submacular thrombus in 15 patients. Following a three-port vitrectomy and subretinal tPA injection (0.1 ml) via a 30 gauge needle, blood was evacuated after enzymatic dissolution for 20 minutes. Two injections were required in some cases. Nine women and six men were treated (mean age 75.5 +/- 8.6 years). Duration of symptoms ranged from 2 days to 8 weeks. One case was due to a retinal macroaneurysm, the others to age-related macular degeneration. Vision improved in 13 patients and remained the same or deteriorated in 2 (mean follow-up 11 +/- 4.9 months). Well-defined subretinal neovascular membranes were identified in 2 patients and occult neovascularisation suspected in 2 others. A cataract developed in 1 case and retinal detachments in 2 others; all were treated successfully. The poor visual prognosis associated with submacular haemorrhage may be obviated by the use of the technique we describe.

Choroidal blastomycosis. A report of two cases.

PURPOSE: To review the presentation and course of choroidal blastomycosis, a rare chorioretinal mycotic infection, which results from disseminated blastomycosis. METHODS: Two cases of disseminated blastomycosis with ocular infection limited to the choroid are presented. Each patient was diagnosed through biopsy of skin lesions demonstrating the characteristic histologic features and the budding yeast. RESULTS: Systemic evaluation revealed extensive disseminated disease with involvement of the eye, lung, skin, bone and joint, central nervous system, and genitourinary system. Both patients were successfully treated with intravenous amphotericin B with elimination of ocular and systemic disease. CONCLUSION: Although rare, blastomycosis can result in choroidal mycotic infection in immune competent individuals. Tissue biopsy to confirm the diagnosis and extensive systemic evaluation are required.

Significance of Bruch's membrane in the creation of iatrogenic chorioretinal venous anastomosis.

Iatrogenic retinal to choroidal vein anastomoses, as a method of bypassing retinal venous occlusions has been reported in dogs in which Bruch's membrane is poorly formed. In order to determine whether chorioretinal venous anastomoses can be induced in an animal with a Bruch's membrane that is well developed as in humans, pigmented rats were chosen. A high intensity, small spot size argon green laser beam of 514 nm was used to induce the anastomosis. Three out of 5 rat eyes developed a retinal vein to choroidal vein anastomosis. The success rate of iatrogenic retinal to choroidal vein anastomoses in the rat was comparable to that obtained in the dog. This study suggests that Bruch's membrane was not significant in the creation of an iatrogenic chorioretinal venous anastomosis.