Detecting AMD with multiply scattered light tomography.

PURPOSE: to use a novel technique, Multiply Scattered Light Tomography (MSLT), to provide a comfortable, rapid, and noninvasive method for detection and management of Age-related Macualar Degeneration. METHODS: two patient groups were studied in clinical settings with MSLT and confocal scanning laser tomography. In Poway, CA, 21 retinal patients underwent tomography, and the 17 patients with suspicion of exudation also had ICG. An Angio-Scan (Laser Diagnostic Technologies, Inc.) was used to provide simultaneous fundus reflectance and ICG imaging. In Methuen, MA, 20 retinal patients underwent tomography with fluorescein angiography for suspicion of exudation. The MSLT was based on the TopSS (Laser Diagnostic Technologies, Inc.), with a Vertical Cavity Surface Emitting Laser array at 850 mm as the illumination source. The central laser produced confocal images. The surrounding lasers produced multiply scattered light images. RESULTS: MSLT emphasized structures beneath the retina such as drusen, choroidal new vessel membranes, and pigment epithelial detachments. Exudation seen on angiography was visualized by MSLT as topographical structures with distinct borders. Superficial structures, e.g., cysts and epiretinal membranes, were visualized in 850 nm images. DISCUSSION: confocal tomography and MSLT provided a rapid, noninvasive method to detect and localize macular degeneration and pathological structures found in eyes of older patients.

Complications of surgery for subfoveal choroidal neovascularization.

Advancing surgical techniques have made the surgical excision of subfoveal CNV possible in all cases. However, serious surgical complications lead to a limited visual outcome in many cases. The major complications that cause poor visual outcome are related to poor case selection and include injury to the RPE, with secondary atrophy of the choriocapillaris and damage to the neurosensory retina, and a high rate of persistent or recurrent CNV. Patients with POHS have localized disease of the RPE-Bruch's membrane complex and typically have CNV growing between the RPE and neurosensory retina (type 2 CNV). These patients have the best visual prognosis postoperatively because of the potential for maintaining native RPE beneath the fovea. Patients with AMD typically have CNV growing beneath the RPE (type I CNV). These patients are poor surgical candidates because the surgical excision of type I CNV is almost always associated with débridement of native subfoveal RPE and a poor visual outcome. Presently, all surgical studies have been retrospective and are characterized by limited follow-up. Therefore, whether surgical excision of subfoveal CNV is beneficial as compared to mere observation is uncertain. A large, randomized, prospective study currently is being performed. These Submacular Surgery Trials will attempt to determine whether these surgical procedures are more efficacious than observation and whether the benefits outweight the risks of surgery in these patients.

Autofluorescence distribution associated with drusen in age-related macular degeneration.

PURPOSE: To determine whether drusen in patients with age-related maculopathy and macular degeneration (ARM/AMD) are associated with focal changes in retinal pigment epithelium (RPE) lipofuscin fluorescence. METHOD: A new autofluorescence imaging device was used to study lipofuscin distribution associated with individual drusen in 20 patients with ARM/AMD. Paired monochromatic and autofluorescence fundus images were used for detailed analysis of the topography of autofluorescence at specific sites containing drusen. In four eyes, image analysis was used to compare the spatial distribution of the autofluorescence with the location of drusen and to quantify the autofluorescence distribution over individual drusen (54 drusen). REsuLTs. A specific pattern of autofluorescence was frequently found to be spatially associated with hard drusen and soft drusen between 60 and 175 microm in size. The pattern is characterized by a central area of decreased autofluorescence surrounded, in most cases, by an annulus of increased autofluorescence. The location of this pattern was highly correlated with the position of individual distinct drusen. The central low autofluorescence focus was on average 16% below the surrounding background, and the annulus, when present, was on average 6% more fluorescent than the background. Soft drusen larger than 175 microm and confluent soft drusen show either multifocal areas of low autofluorescence or a more heterogeneous distribution. CONCLUSIoNs. Autofluorescence imaging permits measurement of RPE lipofuscin at specific sites. RPE overlying drusen have altered autofluorescence, suggesting changes in RPE health.

Foveal cone photopigment distribution: small alterations associated with macular pigment distribution.

PURPOSE: To map the photopigment distribution of central foveal cones in healthy adult subjects before potential onset of age-related macular degeneration. To compare alterations in cone photopigment distribution to those of macular pigment and examine those loci for subretinal changes. METHODS: Eleven healthy subjects (age range, 31-59 years) underwent reflectometry with a scanning laser ophthalmoscope. The difference in cone photopigment density in the fovea was mapped for the long-wavelength- and middle-wavelength-sensitive cones, using 594-nm light. Macular pigment was mapped with 488-nm and 514-nm light. Subretinal changes were investigated with infrared imaging (830-860 nm). RESULTS: Most subjects had small alterations in the regularity of their foveal cone photopigment distribution. Alterations were spatially related to macular pigment alterations but not to the presence of subretinal defects. Subjects were classified into three groups according to the type of alterations in the regularity of pigment distributions: central peak of photopigment and macular pigment, small foveal alterations, and broad distribution with missing central peak of photopigment or macular pigment. The resultant groups differed significantly in age, 43, 46, and 59 years, for groups 1, 2, and 3, respectively (P < 0.05). CONCLUSIONS: Small alterations in the distributions of foveal cone photopigment or macular pigment were found that varied among the subjects. Larger alterations in older subjects may indicate changes in foveal architecture with age, including potential vulnerability of central cones before the onset of clinically significant changes in the retinal pigment epithelium.

A newly recognized maculopathy: benign symmetric oval-shaped foveal depigmentation.

PURPOSE: To characterize a newly recognized maculopathy, benign foveal depigmentation. METHODS: Three patients with unusual foveal depigmentation were prospectively studied. RESULTS: The patients were referred with a diagnosis of Stargardt's macular dystrophy. Ophthalmic examination revealed discrete, bilateral, symmetric, oval foveal depigmentation. This appeared to be at the level of the retinal pigment epithelium. These patients were followed for up to ten years with stable vision and no change in lesion size. CONCLUSIONS: Benign foveal depigmentation is a maculopathy which has discrete, bilateral, symmetric, horizontally oval foveal depigmentation at the level of the retinal pigment epithelium. This appears to be visually benign.

Effect of optic nerve head drusen on nerve fiber layer thickness.

OBJECTIVE: The purpose of the study was to evaluate the effect of optic nerve head drusen (ONHD) on nerve fiber layer (NFL) thickness by visual field testing, red-free photography of NFL, and optical coherence tomography (OCT). DESIGN: The study design was a prospective clinical study. PARTICIPANTS: Twenty-three eyes of 15 consecutive patients with ONHD and 27 eyes of 27 age-matched control subjects participated. INTERVENTION: Ophthalmologic examination, color and red-free photography, automated Humphrey visual field testing, and OCT were performed. Each of the drusen study eyes were graded on a scale of 0 to III based on the amount of visible ONHD. Grade 0 represented the absence of clinically visible ONHD, and grade III represented an optic nerve head with abundant drusen. MAIN OUTCOME MEASURES: Findings from clinical evaluation and color optic nerve head photographs and NFL evaluation by red-free photography, visual fields, and OCT were measured. RESULTS: The number of study eyes with visual field defects increased with the higher grade drusen discs, corresponding both with progressively thinner NFL measurements by OCT and NFL loss shown by NFL photography. The NFL evaluation showed NFL thinning by red-free photography in 12 (71%) of 17 eyes with visible drusen (grades I-III discs) and visual field defects in 9 (53%) of 17 eyes in this group. By OCT measurements, the superior and inferior NFLs were significantly thinner in the eyes with visible ONHD compared with those of control eyes in the superior quadrant (P < 0.001) and inferior quadrant (P = 0.004). Compared with grade 0 discs, grades I through III discs showed statistically significant thinning of the NFL superiorly (P < 0.001). No statistical significant thinning of the NFL was seen in grade 0 discs compared with those of control subjects. CONCLUSIONS: Optical coherence tomography is able to detect NFL thinning in eyes with ONHD and appears to be a sensitive and early indicator of NFL thinning. Increased numbers of clinically visible ONHD correlated with NFL thinning shown by OCT measurements and both visual field defects and NFL loss seen by red-free photography.

Melanocytomas of the optic nerve and uvea.

Melanocytomas are an example of changing attitudes toward clinical management of intraocular tumors. They also might exemplify the power of pathological examination and follow-up in patient care and treatment. Prior to the observations of Zimmerman [10], most patients with melanocytomas underwent enucleation. Today, these patients are followed up conservatively and continue to enjoy vision. Melanocytomas are fairly uncommon tumors found more often in blacks and hyperpigmented individuals than in whites. Women are slightly more likely to have this tumor than are men. Melanocytomas are uniformly densely hyperpigmented lesions found on the optic nerve, choroid, ciliary body, and iris and are benign, stationary tumors that seldom cause symptoms or secondary complications. In patients with papillary melanocytomas, the most common visual disturbance is enlargement of the blind spot. With larger tumors, an afferent pupillary defect may be noted. Ciliary body and iris tumors may cause secondary anterior segment complications such as glaucoma, hyphema, or ectopia. Dispersion of pigment by melanocytomas is common and should not necessarily be interpreted as a sign of malignant transformation. Ancillary tests such as fluorescein angiography, ICG angiography, ultrasonography, CT, MRI, and the 32P test are of little clinical benefit in differentiating between melanocytomas and malignant melanomas and may lead to erroneous conclusions. Treatment for melanocytomas is conservative, its mainstay being serial clinical examinations, fundus photography, and visual field examinations to record tumor size and document growth. Lesions that grow rapidly may have transformed to a malignant melanoma and should be treated accordingly.

Choroidal osteoma.

The choroidal osteoma is a benign, ossifying tumor of the choroid that typically is found in young, healthy women in the second or third decade of life. Its pathogenesis is unknown. This tumor is clinically unilateral in 75% of cases and tends to be located in the juxtapapillary region. Choroidal neovascularization may occur in up to one-third of cases. The choroidal osteoma must be differentiated from other intraocular tumors as well as cases of dystrophic and metastatic calcification. Ultrasonography and computed tomography may help in the diagnosis by demonstrating a calcified plaque at the level of the choroid. Fluorescein angiography and ICG videoangiography may demonstrate choroidal neovascularization, which may be amenable to treatment by laser photocoagulation.

Deep retinal vascular anomalous complexes in advanced age-related macular degeneration.

PURPOSE: The authors describe the clinical characteristics of a group of patients with age-related macular degeneration (AMD), deep retinal vascular anomalous complexes (RVACs), advanced Bruch membrane changes, and severe visual loss. Based on clinical evaluation and imaging studies, the authors hypothesize the cause of such retinal vascular formations. PATIENTS AND METHODS: The authors quantified an initial case series of 6 patients and expanded it to 11 patients (14 eyes) with AMD and RVACs diagnosed by fluorescein angiography or slit-lamp examination. Associated pigment epithelial detachments (PEDs) of 13 eyes are described. In addition to the clinical and fluorescein angiography descriptions, infrared imaging and indocyanine green angiography were used to characterize more recently described RVACs and fellow eyes. RESULTS: Each study eye had a clearly defined anastomosis connecting the retinal circulation to a vascular complex in the deep retina. The RVACs associated with PEDs assumed a more central location than did typical choroidal neovascularization associated with PEDs. In seven eyes with RVACs, there were clinically recognizable retinovascular findings: intraretinal hemorrhages, telangiectasia, or microaneurysms. Legal blindness occurred in 9 of 11 patients. CONCLUSION: These results indicate that retinovascular changes can be associated with nondisciform AMD. The authors speculate that neurodegenerative changes and hypoxia may lead to such changes, the RVAC being a more advanced finding. Closure of an RVAC with photocoagulation is difficult, perhaps because of its higher blood flow. The visual outcome is poor, not only because of the advanced state of the underlying AMD, but also because of the exudative nature of the RVAC.

Infrared imaging of sub-retinal structures in the human ocular fundus.

The interaction of infrared light with the human ocular fundus, particularly sub-retinal structures, was studied in vivo. Visible and infra-red wavelengths and a scanning laser ophthalmoscope were used to acquire digital images of the human fundus. The contrast and reflectance of selected retinal and sub-retinal features were computed for a series of wavelengths or modes of imaging. Near infrared light provides better visibility than visible light for sub-retinal features. Sub-retinal deposits appear light and thickened; the optic nerve head, retinal vessels, and choroidal vessels appear dark. Contrast and visibility of features increases with increasing wavelength from 795 to 895 nm. Optimizing the mode of imaging improves the visibility of some structures. This new quantitative basis for near infrared imaging techniques can be applied to a wide range of imaging modalities for the study of pathophysiology and treatment in diseases affecting the retinal pigment epithelium and Bruch's membrane, such as age-related macular degeneration.

Protracted posttraumatic optic disc swelling.

BACKGROUND: Optic disc swelling is a rare sequela of blunt ocular trauma. METHODS: The authors examined three young patients who had an unusual post-traumatic optic neuropathy in which protracted swelling of the optic nerve head was the salient clinical feature. RESULTS: Associated choroidal ruptures in two patients suggested a contrecoup mechanism of injury to the optic nerve at its junction with the globe. All patients had partial recovery of vision over months, concurrent with resolution of the nerve head swelling and development of optic disc pallor. CONCLUSION: Despite its protracted course, posttraumatic optic disc swelling appears to be associated with a favorable prognosis for visual recovery.

[In vivo fundus fluorescence measurements in patients with age related macular degeneration]. / In-vivo-Fundus-Fluoreszenzmessungen bei Patienten mit altersabhängiger Makuladegeneration.

UNLABELLED: This study was performed to measure and characterize the intrinsic fluorescence of the ocular fundus in patients with age-related macular degeneration (AMD). METHOD: Fluorescence spectral measurements from discrete retinal locations were made using the fundus spectrophotometer with excitations at 470 and 510 nm. Two normal subjects and seven patients with different stages of AMD were investigated. RESULTS: The spectral characteristics of fundus fluorescence are consistent with those of lipofuscin in the retinal pigment epithelium (RPE). The fluorescence spectrum is broad, with a maximum at about 620 nm. The shape and intensity of the fluorescence spectra are affected by age, site of measurement, pathology, ocular media absorption, and excitation wavelength. Spectra from areas with drusen reveal an additional fluorophore, with maximum around 560 nm, probably emanating from drusen and Bruch's membrane. Measurements in atrophic reveal a decrease of lipofuscin fluorescence and/or a contribution likely due to choroidal and sclera collagen fluorescence. Fluorescence from lipofuscin is more efficiently excited at 510 nm, whereas that of drusen and subretinal structures is relatively more efficient with 470 nm excitation, allowing for discrimination of various fluorophores. CONCLUSION: The spectral characteristics of RPE lipofuscin could be identified and quantified in AMD patients. In addition, the spectra are affected by other fluorophores such as drusen and choroid contributions in atrophy. Fluorescence spectra measurements in AMD patients allow for discrimination of lipofuscin fluorescence, drusen fluorescence, and choroidal or scleral fluorescence. The non-invasive measurement of lipofuscin and drusen fluorescence in AMD may be helpful in monitoring the disease, understanding its evolution, and testing therapeutic concepts.

In vivo measurement of lipofuscin in Stargardt's disease--Fundus flavimaculatus.

PURPOSE: Several histopathologic studies have concluded that Stargardt's disease (Fundus flavimaculatus) is associated with abnormally high levels of lipofuscin-like material in the retinal pigment epithelium. The purpose of this study was to determine whether this material has the same fluorescence characteristics as lipofuscin in vivo and whether noninvasive measurements identify a significant elevation in this material. METHODS: Five patients with autosomal recessive Stargardt's disease were included in this study, as were 45 healthy controls. All patients had the angiographic dark choroid sign. The intensity and emission spectra of lipofuscin fluorescence were measured by noninvasive fundus spectrophotometry at 7 degrees temporal to the fovea. RESULTS: The fluorescence intensities in the five patients with Stargardt's disease were significantly higher (P < 0.0001) than those observed in normal subjects of the same age. The emission spectra in the patients are similar in shape to those measured in normals, but flecks appear to shift the spectra toward shorter wavelengths. CONCLUSIONS: The spectral characteristics of the fluorophore observed in patients with Stargardt's disease are consistent with those of retinal pigment epithelial lipofuscin. These patients have abnormally high levels of lipofuscin, confirming previous histopathologic observations. Noninvasive retinal pigment epithelial lipofuscin measurements may be a useful adjunct in the diagnosis of Stargardt's disease.-F. flavimaculatus.

In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics.

PURPOSE: To characterize the intrinsic fluorescence (autofluorescence) of the human ocular fundus with regard to its excitation and emission spectra, age relationship, retinal location, and topography, and to identify the dominant fluorophore among the fundus layers. METHODS: Using a novel fundus spectrophotometer, fluorescence measurements were made at 7 degrees temporal to the fovea and at the fovea in 30 normal subjects and in 3 selected patients. Topographic measurements were made in 3 subjects. Ex vivo measurements of fluorescence of human retinal pigment epithelium (RPE) were obtained and compared to in vivo data. RESULTS: Fundus fluorescence reveals a broad band of emission between 500 and 750 nm, a maximum of approximately 630 nm, and optimal excitation of approximately 510 nm. Exhibiting a significant increase with age, this fluorescence is highest at 7 degrees to 15 degrees from the fovea, shows a well-defined foveal minimum, and decreases toward the periphery. In vivo fluorescence spectra are consistent with those obtained ex vivo on human RPE. Measurements with short wavelength excitation are strongly influenced by ocular media absorption and reveal an additional minor fluorophore in the fovea. CONCLUSIONS: Spectral characteristics, correlation with age, topographic distribution, and retinal location between the choriocapillaris and the photoreceptors suggest that the dominant fundus fluorophore is RPE lipofuscin. The minor fluorophore is probably in the neurosensory retina but has not been identified.

Light damage to the eye.

The effects of light on the eye are being increasingly recognized. In addition to visible radiation, we are constantly exposed to infrared and ultraviolet radiation throughout life. Acute light damage such as sunburn of eyelids, photokeratitis and solar retinopathy are well recognized and fairly obvious. The effects of chronic light exposure have been more controversial. Recent epidemiologic studies are showing an association between long-term sunlight exposure and ocular diseases such as cataracts, age-related macular degeneration, pterygium and climatic droplet keratopathy. Furthermore, the role of photosensitizers contributing to light-induced ocular damage needs to be kept in mind. The ocular hazard from photosensitizing drugs and sunlight in general is greatest in aphakic eyes that have lost their natural ultraviolet filter (the ocular lens) and in young children, whose own lenses readily transmit ultraviolet light. At present, there is enough evidence to assume that chronic sunlight exposure contributes to ocular disease and to institute preventive measures.

Endophthalmitis caused by the coagulase-negative staphylococci. 1. Disease spectrum and outcome.

PURPOSE: The coagulase-negative staphylococci are the most common causes of postoperative endophthalmitis. This study investigates the variability in the disease spectrum and visual outcome of coagulase-negative staphylococcal endophthalmitis in a large, single-center series. METHODS: Ninety consecutive cases of coagulase-negative staphylococcal endophthalmitis were investigated retrospectively from two time periods, 1978 to 1982 and 1985 to 1987, separated by a transitional period in cataract surgery technique. Using a detailed protocol, inpatient, outpatient, and microbiologic records were analyzed. Six-month visual acuity results were obtained. RESULTS: Diagnosis frequently was delayed, often suspected only after hypopyon development. Thirty-seven percent of patients presented more than 1 week after the inoculating event, and 13% presented after more than 1 month. Variable asymptomatic intervals and gradually worsening inflammatory prodromes are noted. Painless endophthalmitis occurred in 16%. Non-epidermidis infections comprised 28%. With vitrectomy/intraocular antibiotic management, 38% and 68% achieved visual acuities of 20/50 and 20/400, respectively. Overall, 10% of patients developed late retinal detachments. This occurred in only 4% of patients, with endophthalmitis occurring after cataract surgery. CONCLUSION: Ophthalmologists should become familiar with the emerging concepts of delayed-onset, chronic, and often painless endophthalmitis in which the coagulase-negative staphylococci play a prominent role.

Endophthalmitis caused by the coagulase-negative staphylococci. 2. Factors influencing presentation after cataract surgery.

PURPOSE: This study, comprising 60 patients with coagulase-negative staphylococcal endophthalmitis which occurred after cataract surgery, was designed to define the variation in disease presentation and visual outcome and to evaluate statistically the role of the primary surgery and its management. METHODS: An intensive evaluation of microbiological, inpatient, outpatient, and cataract surgery charts was made retrospectively using a standardized protocol. The predictive value of surgical, iatrogenic, and clinical factors was analyzed for their influence on defined aspects of the disease pattern and of the visual results using multiple regression models, via a stepwise technique. RESULTS: There was commonly a significant asymptomatic latent period after cataract surgery. The median diagnostic delay was 7 days; 22% of patients presented after 2 weeks and 12% after 1 month. Symptoms progressed longer than 3 days in 25% of patients. Ten percent had no pain. Clinical variation proved largely unrelated to cataract surgery events and postoperative management; bacterial factors were implicated. Good visual outcome was associated statistically with intensive topical corticosteroid in the symptomatic period, but was negatively associated with operative subconjunctival corticosteroid. CONCLUSIONS: The clinical variation in cases of postoperative coagulase-negative staphylococcal endophthalmitis poses particular problems for diagnosis in the outpatient setting. Surgical and perioperative events (except corticosteroid use) probably can be disregarded in studies of endophthalmitis management.