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In a 65-year-old woman with a choroidal melanoma of the choroid a unilateral pseudoretinitis pigmentosa was detected by ophthalmoscopy. Histological examination revealed a mixed-cell type of malignant melanoma with melanophages and proliferation of pigment epithelium spreading over the inner surface of the retina, with seedings into the vitreous.
Forty-four of the 262 pupils at the school for blind and visually handicapped children in Nuremberg, i.e., 17%, suffer from sequelae of retinopathy of prematurity (ROP); this condition is currently top of the list of causes of blindness. The risk factors involved were identified by analyzing 294 histories of premature children born between 1981 und 1984. In the case of 16 children, ophthalmoscopic criteria were taken from the 1984 international classification. The data of the children with ROP, at birth and at the time when ROP developed, were recorded on a prognosis card, in each case between the child's absolute age (abscissa) and birthweight in g (ordinate). In this way it was possible to read off the critical phase of retinal development for each newly examined child. This card facilitates monitoring, the provision of forensic evidence, the timing of ophthalmoscopy during critical phases of retinal development, and may also enable further relationships to be detected.
This atlas is the first publication dealing with the clinical significance of the light reflexes of the fundus. The mechanism and the conditions for the occurrence of light reflexes in ophthalmoscopy are described. A classification of the light reflexes is presented, dividing them into normal and pathologic groups. The normal light reflexes - foveolar, macular, areal, paravasal, streaks of light on the vessels - and their abnormal variations in different diseases of the fundus are described. The pathologic light reflexes - fanlike, focal, peripapillary, linear, stationary, metallic, crystalline - and their diagnostic significance are discussed. Practical recommendations are given for assessing pathologic changes in the retina and the optic disk from the appearance of the light reflexes. Finally the manifestation of light reflexes as a characteristic of some diseases of the fundus is pointed out.
PURPOSE: Meningococcal septicemia is associated with coagulopathy and hemorrhagic tendency. We carried out this study to determine the incidence of retinal hemorrhages in meningococcal septicemia. METHODS: This was a prospective study involving all children admitted to the Sheffield Children's Hospital, Sheffield, England, with a diagnosis of meningococcal septicemia. Confirmation of meningococcal infection was by blood culture or DNA analysis using polymerase chain reaction. The children underwent ocular examination including dilated fundus examination by direct and indirect ophthalmoscopy. Details of their coagulation status were also obtained. RESULTS: Twelve children (mean age, 4.5 years) with a confirmed diagnosis of meningococcal septicemia were included. All children had coagulopathy. Retinal hemorrhages were found in 5 children (42%). The disease was fatal in 3 children. Group C meningococcus was responsible for the infection in all those with retinal hemorrhages and those with fatal outcome. CONCLUSIONS: Retinal hemorrhage is a common feature in meningococcal septicemia. Ophthalmic evaluation should be part of the assessment of children with meningococcal septicemia. Future studies on meningococcal disease should include retinal hemorrhage as another parameter in the assessment. This should help us to understand the role of retinal hemorrhage in the prognosis of this serious disease.
OBJECTIVE: To determine whether regional cerebral parenchymal injury patterns correlate with the distribution of retinal hemorrhages after inflicted head injury. STUDY DESIGN: Retrospective case series of funduscopic photographs and serial computerized tomographic imaging of 14 children with confirmed inflicted head injury. MAIN OUTCOME MEASURES: Retinal Hemorrhage Score per eye and per subject, visual field examination, regional patterns of parenchymal injury on computerized tomographic scans and necropsy, and retinal/optic nerve sheath hemorrhage distribution at necropsy. RESULTS: Ten of 14 children had retinal hemorrhages (71%); 90% were asymmetric (mean retinal score, 4.89 vs 2.56; P=.006). Retinal hemorrhages were maximal on the side of greatest cerebral injury in seven of 10 children initially. Subsequent imaging asymmetry predicted retinal hemorrhage distribution in all eight survivors. Children's Coma Scores, apnea or cardiorespiratory arrest, initial hemoglobin, and plasma glucose concentration did not predict laterality. Asymmetry was greatest if dilated ophthalmoscopy was performed during the first 24 hours (P=.03). Visual outcome was poor; three had homonymous hemianopia and four had cortical visual loss, all correlating with parenchymal atrophy patterns. CONCLUSION: The distribution of retinal hemorrhages after inflicted head injury correlates with acute and evolving regional cerebral parenchymal injury patterns.
PURPOSE: To investigate the effect of fluorescein on human fetal neural retina and adult rat retina; and to use fluorescein to map the area of subretinal transplantation. METHODS: In vitro: Human fetal neural retina (8 to 14 weeks gestational age) was incubated in 0.03% fluorescein in Dulbecco's Modified Eagles Medium (DMEM) or DMEM alone for 30 min. Viability was determined using the trypan blue exclusion test, and results were compared. Effects of the fluorescein on cell morphology were assessed by observation of primary cultures for 1 week. In vivo: Human fetal neural retina was mechanically dissociated in 0.03% fluorescein in DMEM and transplanted to the subretinal space of immunosuppressed rats. To control for the effect of fluorescein on the grafted tissue, transplants were also performed in DMEM only. After transplantation, indirect ophthalmoscopy and true color fundus photography were performed to document the area covered by the transplant. One month after transplantation, the appearance of grafts exposed to fluorescein was compared to those that were not, at the light microscopic level. RESULTS: In vitro: Exposure of human fetal neural retina to fluorescein had no effect on viability. Similarly, in tissue culture, the fluorescein-exposed cells exhibited the same phenotype as the controls. In vivo: Immediately after transplantation the graft site was clearly outlined within the subretinal area and fluoresced intensely. There were no traces of the dye 2 h after transplantation. Cells that were transplanted with fluorescein survived transplantation, and one month after transplantation could be seen forming subretinal grafts. No differences were noted between these and control grafts. CONCLUSIONS: Fluorescein is an effective dye for immediate and transient localization of trans-scleral transplants to the subretinal space. It allows mapping of the area covered by the injection without interfering with the viability and differentiation of the transplanted cells. It allows unequivocal photo- and video-documentation in both the albino and pigmented fundi. It is already FDA approved for many other extra- and intraocular studies and now has directly been shown to be non-toxic to both human fetal neural retina and adult rodent retina.
PURPOSE: To create a model of proliferative vitreoretinopathy (PVR) using retinotomy with vitrectomy, cryotherapy, and platelet-rich plasma (PRP) injection, which more closely resembles the human pathophysiologic condition. METHODS: One hundred and twenty albino rabbits were divided into 10 groups of 12 rabbits each and underwent the following procedures: group 1, vitrectomy; group 2, cryotherapy; group 3, PRP intravitreous injection; group 4, retinotomy; group 5, retinotomy and vitrectomy; group 6, retinotomy and cryotherapy; group 7, retinotomy and PRP injection; group 8, retinotomy, vitrectomy, and cryotherapy; group 9, vitrectomy, cryotherapy, and PRP injection and group 10, retinotomy, vitrectomy, cryotherapy, and PRP injection. All animals underwent follow-up examinations with indirect ophthalmoscopy and fundus photography on days 1, 3, 7, 10, 14, 21, and 28 after the procedure(s). Retinal changes were categorized according to the classification of Fastenberg et al. At the end of the experiments, the eyes were enucleated, and examined under light and electron microscopy. RESULTS: No retinal detachments (RDs) were observed in groups 1, 2, 4, 5, 6, and 8. RDs of varying severity were observed in group 3 (n = 1), group 7 (n = 2), group 9 (n = 6), and group 10 (n = 12). Light and transmission electron microscopy confirmed the findings. CONCLUSIONS: Combining retinotomy with vitreous removal, cryotherapy, and PRP injection creates an efficient and different model of PVR that produced RD in 100% of rabbit eyes.
PURPOSE: To determine leukocyte kinetics in the retinal microcirculation of streptozotosin-induced diabetic rats. METHODS: Rats were made diabetic with intraperitoneal injection of streptozotosin. For one month after injection, the alteration of the velocity and plugging of leukocytes were investigated using acridine orange, which stains leukocytes, and scanning laser ophthalmoscopy. Blood plasma protein levels, such as fibrinogen and alpha1- and alpha2- globulin, were also measured. RESULTS: Throughout the observational period, mean leukocyte velocity was similar between diabetic (1.53+/-0.45 mm/sec) and age-matched control (1.58+/-0.23 mm/sec) rats, but the coefficient of variation of the velocity in the diabetic rats was twice as large as that in the control rats. Plugging was increased in a sigmoidal fashion and saturated for 5 weeks or later. No differences were seen in plasma protein levels between groups. CONCLUSIONS: Within one month of the hyperglycemic condition, the velocities of leukocytes in capillaries were more varied and the leukocytes were plugged time-dependently. This action occurred not because the blood fibrinogen and globulin levels were altered, but because of the leukocyte-endothelium interaction. In streptozotosin-induced diabetic rats, retinopathy usually cannot be found during the fundus examination and fluorescein angiography. In the level of the microcirculation, however, some of the disorders have already occurred.
PURPOSE: Vascular endothelial growth factor (VEGF) causes widespread retinal vascular dilation, produces breakdown of the blood-retinal barrier, and is implicated in ocular neovascularization (NV). Basic fibroblast growth factor (bFGF) also has been implicated in the production of ocular NV. This study was performed to investigate the ability of simultaneous sustained intravitreal release of both VEGF and bFGF to induce robust retinal NV in the rabbit. METHODS: Intravitreal implantation of sustained-release Hydron polymeric pellets containing both 20 microg of VEGF and 20 microg of bFGF was performed on adult male Dutch belted rabbits. In other animals either 20 microg or 50 microg bFGF-containing pellets was implanted intravitreally; also, either 20 microg VEGF or 50 microg VEGF-containing pellets was implanted. Control rabbits received either blank polymeric pellets or a pellet containing 30 microg bovine serum albumin. Eyes were examined by indirect ophthalmoscopy after surgery at 24 hrs, 48 hrs, 4 days, 7 days, 14 days, 21 days, and 28 days. Findings were documented by color fundus photography and fluorescein angiography (FA). Eyes were enucleated and prepared for histologic analysis at 28 days following intravitreal implantation of the VEGF/bFGF-containing pellets. RESULTS: In all eyes implanted with VEGF/bFGF pellets, dilation and tortuosity of existing blood vessels were observed within 48 hrs after pellet implantation. The progression of retinal vascular changes was rapid and occurred over the entire optic disk and medullary rays between 4 and 7 days. Hemorrhage occurred as early as 14 days after VEGF/bFGF pellet implantation. In eyes with massive hemorrhage, total traction retinal detachment developed after the second week. The presence of abnormal tissues at the vitreo-retinal interface within 28 days was demonstrated by light microscopy while FA showed profuse leakage of dye from anomalous vessels within the first week. Neither bFGF-exposed eyes nor control eyes showed any vascular changes. Eyes that received only VEGF-containing pellets exhibited tortuosity of existing vessels, but neither hemorrhaging nor retinal detachment occurred. CONCLUSIONS: These results demonstrate that retinal vascular changes leading to hemorrhaging is produced rapidly in the rabbit by simultaneous intravitreal release of both VEGF and bFGF. Understanding how these growth factors induce retinal NV may suggest novel therapeutic treatment strategies.
PURPOSE: Trovafloxacin is an expanded spectrum, newer-generation fluoroquinolone antibiotic with improved Gram-positive and anaerobic activity compared with existing quinolones, while maintaining Gram-negative activity comparable to ciprofloxacin. Given its broad spectrum of activity, trovafloxacin may have potential use for treatment of acute bacterial endophthalmitis. This study examined the toxicity of intravitreally administered trovafloxacin in the pigmented rabbit eye. METHODS: Doses of trovafloxacin ranging from 12.5 microg to 1000 microg were injected into the mid-vitreous of Dutch Belted rabbit eyes. Clinical examination was performed at 1, 3, and 14 days following injection. Animals were sacrificed and eyes were enucleated 14 days following injection. Light microscopy (LM) and transmission electron microscopy (TEM) studies of the optic nerve head, medullary ray, and inferior retina were performed to determine toxicity. RESULTS: At intravitreal doses of 500 microg and less, no toxicity was observed at the ophthalmoscopic or light microscopic level. By TEM, a dose-dependent increase in injury to retinal pigment epithelium, photoreceptors, and nerve fibers in the optic nerve head and medullary ray was observed from 50 microg to 500 microg. No toxicity was noted at doses of 12.5 microg and 25 microg. At doses of 750 microg and above, edema of the medullary ray was noted on ophthalmoscopy. Swelling of the peripapillary medullary ray and necrosis of the inferior retina were evident on LM. CONCLUSION: Intravitreal trovafloxacin doses of 50 microg and higher in the pigmented rabbit eye cause retinal and nerve fiber injury. Intravitreal doses 25 microg and lower appear to be safe, with no evidence of ocular toxicity.
Tacrolimus (FK506) is effective in Japanese endogenous posterior uveitis (EPU), but there is limited data on its role in refractory EPU where cyclosporin A (CsA) toxicity/resistance develops. This open prospective clinical study aimed to assess the efficacy and adverse effects of low-dose FK506 therapy in western patients with refractory EPU where CsA resistance or toxicity has developed. Patients with CsA resistant/toxic EPU were started on low-dose (< 0.10 mg/kg/day) FK506 therapy. Immunosuppressive efficacy was assessed by visual acuity, binocular indirect ophthalmoscopy (BIO) scores, and change in clinical features. Adverse effects were assessed by routine biochemical tests (including serum creatinine) and symptoms. Seven patients (13 eyes), aged (mean +/- SD) 37.5 +/- 14.8 years, were recruited with previous CsA nephrotoxicity as the main indication and prior duration of EPU of (mean +/- SD) 13.1 +/- 7.3 years. Behçet's disease was the commonest diagnosis. FK506 therapy was maintained at 0.06 +/- 0.02 mg/kg/day, trough level of 8.7 +/- 1.8 ng/ml, in combination with low-dose prednisolone (0.11 +/- 0.04 mg/kg/day) in all patients for a mean duration of 8.7 months (range 1.0-17.7). From baseline (for 11 eyes with meaningful follow-up), visual acuity was maintained in nine eyes and BIO score improved in nine eyes. No major adverse effects developed, with only a 7.5 +/- 6.5% maximum increase in serum creatinine in patients with previous CsA-induced nephrotoxicity. Minor adverse effects (especially mild hyperglycaemia and neurological symptoms) were common and usually well tolerated, except for two patients in whom drug withdrawal was necessary, thus producing therapeutic failure. Low-dose FK506 is effective in refractory EPU as CsA-rescue therapy, and should be considered earlier in the evolution of refractory EPU.
BACKGROUND AND PURPOSE: Screening in a primary care setting could be an effective method for detection of eye disease. This study was designed to evaluate a questionnaire and a battery of tests for their performance in eye disease screening at a primary care clinic. METHODS: 405 patients aged 40 years or older were interviewed and received a comprehensive eye examination including visual acuity and visual field testing, tonometry, slit-lamp examination, dilated fundus examination and photography. Sensitivity and specificity for the identification of eye disease were calculated for each test and various combinations of tests. RESULTS: A questionnaire-based algorithm for detection of overall eye disease was sufficiently sensitive (90%) but less specific (44%) than an ideal screening test. Distance visual acuity with presenting correction of < or = 20/40 had a sensitivity of 61% and specificity of 72%. A dilated fundus examination had a sensitivity of 79% and specificity of 82%. In screening for glaucoma, tonometry was ineffective (sensitivity = 27% and specificity = 96%), while visual field testing by suprathreshold screening had a sensitivity of 70% and specificity of 67%. Among a variety of combinations, a two-stage strategy with the questionnaire as a first-stage and visual acuity and ophthalmoscopy as second-stage tests provided the best balance of sensitivity (83%) and specificity (76%). CONCLUSION: Among currently available ophthalmic tests, an eye examination including a thorough fundus examination is critical in detection of eye disease. A five-item questionnaire may be useful to identify patients at high risk in primary care practice. More effective tests are needed to improve performance of eye disease screening.
PURPOSE: To investigate the subretinal toxicity profile of the ribozyme to the proliferating cell nuclear antigen (PCNA-Rz) and 5-fluorouracil (5-FU), as well as the highest nontoxic subretinal dose of the mixture of the two agents in rat eyes. METHODS: Brown-Norway rats received subretinal injections of 1 microg, 10 microg, and 100 microg/microl PCNA-Rz and 0.06 microg/microl, 0.3 microg/microl, and 1.5 microg/microl 5-FU in the right eyes, and the left eyes were injected with H-BSS as control. Each dose was tested on 5 eyes in a 5 microl volume. In a second study, a combination of 5-FU (1.5 microg/microL) with varying 10-30-50 microg/microl doses of PCNA-Rz was tested in a regimen of four sequential subretinal injections. Toxicity was monitored by biomicroscopy, indirect ophthalmoscopy, electroretinography (ERG), and histology. RESULTS: The highest nontoxic dose for subretinal PCNA-Rz was 10 microg/microl, whereas 100 microg/microl showed disturbance of pigmentation with corresponding histological changes of retinal photoreceptor loss and retinal pigment epithelium proliferation or irregularities. Subretinal injection of all three doses of 5-FU did not show any toxicity. Serial injections of a mixture of 1.5 microg/microl 5-FU with 10 microg/microl of PCNA-Rz was found to be safe in rat eyes. CONCLUSIONS: Subretinal injections of the combination of PCNA-Rz (10 microg/microl) and 5-FU (1.5 microg/microl) demonstrated to be safe in rat eyes during the course of this study, even with a multiple administration of four injections.
PURPOSE: The lamina cribrosa has been proposed as a site of origin of the optic nerve damage in glaucoma. The purpose of this study was to investigate, in vivo, the clinical features of the lamina cribrosa pores of glaucomatous patients and to relate their morphometric characteristics to the extent of their visual field loss. METHODS: Images of the internal lamina cribrosa surface of 60 glaucomatous patients and 15 normal subjects were acquired, in vivo, using a scanning laser ophthalmoscope (SLO). A purposely developed technique of image processing was employed to objectively evaluate pore morphometry, with particular regard to their geometrical characteristics (circularity and elongation). Visual function was assessed by automated perimetry (Humphrey Field Analyser). RESULTS: Normal subjects showed approximately round lamina pores. In glaucomatous patients, pores become more elongated and less circular with increasing field loss (p = 0.009 and p < 0.001, respectively). CONCLUSIONS: Scanning laser ophthalmoscopy and a new technique of image processing were employed, for the first time, to the investigation in vivo of the lamina cribrosa of glaucomatous patients, in relation to the extent of visual field loss. The results indicated differences in the lamina cribrosa pore morphometry associated with increasing severity of the disease. These changes may represent the result of compressing and shearing forces applied to the laminar plates.
PURPOSE: To describe an unusual case of simultaneous bilateral exudative retinal detachment and peripheral necrotizing retinitis as presenting manifestations of concurrent HIV and syphilis infection. CASE REPORT: A previously healthy 35-year-old Caucasian male was first seen for bilateral sudden visual loss. Ophthalmoscopy showed bilateral exudative retinal detachment involving the posterior pole and a placoid-like area of peripheral necrotizing retinitis in his left eye. Physical examination revealed anal condylomata and aphthous oral lesions. Laboratory investigations confirmed the diagnosis of concurrent HIV and syphilis infection. Ocular lesions resolved in response to anti-syphilitic medication administered for three weeks. DISCUSSION: This case demonstrates the importance of considering syphilis as a cause of atypical retinitis in the HIV-positive population.
AIM: To elucidate the rate of non-response among diabetics (recently diagnosed in rural diabetic screening camps) who were referred for eye examination to detect diabetic retinopathy. METHODS: At diabetic retinopathy screening camps, all patients underwent dilated fundus examination using binocular indirect ophthalmoscopy. RESULTS: Of the 4,111 known diabetics, only 2231(55%) patients attended the diabetic retinopathy screening camps. Likewise, of the 1076 newly detected diabetics, only 125 (11.6%) attended the diabetic retinopathy screening camps. CONCLUSIONS: Non-response of such a magnitude calls for creating greater awareness among masses on diabetes and its microvascular complications. Second, conducting simultaneous diabetes screening and diabetic retinopathy screening camps could minimize the dropout rate.
PURPOSE: To model the natural course of geographic atrophy (GA) in patients with age-related macular degeneration (AMD). METHODS: Data on the natural course of GA were collected in the multi-center, longitudinal, prospective observational FAM study. The size of GA was measured by autofluorescence scanning laser ophthalmoscopy. The natural course of GA is modelled by two different mixed effect models (MEM). Both models are compared with respect to the correctness of the model assumptions, goodness of fit, and predictive behavior. RESULTS: The linear model results in better prediction, the non-linear model is more in agreement with the model assumptions. The non-linear model fits the data for small and large areas of GA better, while the linear model seems to be more adequate for the medial areas. More data will be needed to study the interplay of both models in more detail. CONCLUSIONS: The natural course of GA varies extremely between individuals. However, reliable factors for the explanation of this variability have so far not been established. MEM are useful for describing "inter-individual" as well as "intra-individual" influences without the need for precise knowledge of the influencing factors. Using MEM to evaluate data on the natural history of GA allows one to derive parameter estimates, which could be used to design interventional trials for modes of therapy with a potential to reduce or stop the progression of GA in patients with AMD.
PURPOSE: To investigate the cause of vision loss in patients with ganglioside GM3 synthase deficiency, a newly described rare autosomal recessive infantile-onset symptomatic epilepsy syndrome associated with developmental stagnation and blindness. METHODS: We examined four children from two related Amish sibships. Molecular genetic analysis confirmed inheritance of the founder mutation. Electroretinography and fundus photography were obtained in two patients. RESULTS: Despite an initial suspicion of retinal degeneration, retinal function was found to be preserved in both patients and ERG amplitudes were within normal limits. Ophthalmoscopy showed bilateral optic atrophy in all patients. CONCLUSIONS: Vision loss in GM3 synthase deficiency results from central nervous system and optic nerve involvement. Retinal function appears to be otherwise normal into the teenage years.