Landmark-driven fundus perimetry using the scanning laser ophthalmoscope.

PURPOSE: To present a new method of performing scanning laser ophthalmoscope perimetry that compensates for eye movements so that the correct retinal location is tested even if fixation changes. This allows for accurate testing of patients with central scotomas and for repeating testing longitudinally at the same retinal locations even if central fixation is lost. METHODS: The operator views the retina and selects a retinal landmark, such as a vessel bifurcation, that can be identified easily. A testing strategy is preselected, and the computer saves the landmark and stimulus coordinates. To present each stimulus, the operator positions a cursor over the retinal landmark, and the computer adjusts the site of presentation of the stimulus for any change in landmark position caused by an eye movement. At the conclusion of the testing, the results are displayed in the proper retinal location on a fundus image. RESULTS: Sixty-seven eyes with macular disease were tested with the landmark-driven method, using the same preplanned strategy for each eye for both a bright and a dim stimulus. There was a low rate of inconsistent points (seen with dim but not bright stimuli), and virtually all of these bordered a dense scotoma. Those eyes with more inconsistent points had a significantly greater percentage of dense scotoma points and significantly lower visual acuity. The technique significantly corrected error in retinal localization resulting from large eye movement. There is no significant rotation or magnification change during the procedure, so specifying the change in location of one landmark is sufficient to describe movement of the retina. The technique is rapid and easy to administer to elderly patients and to children. CONCLUSIONS: This technique allows for accurate and repeatable measures of retinal sensitivity in specific locations. It is useful in following change over time. It can be developed further to allow for fully automated, retinally correct testing.

Measuring geographic atrophy in advanced age-related macular degeneration.

PURPOSE: To present a method developed for measuring areas of geographic atrophy (GA) in advanced age-related macular degeneration, METHODS: A microfilm reader projected the 30 degrees fundus photograph of the macula. Retinal landmarks, atrophic areas, and spared areas within the atrophy were traced, without access to drawings of other years. The total atrophic area was calculated, as was the atrophy within a four-disc-area circle entered on the estimated foveal center. The configuration of the atrophy was documented. RESULTS: Avoidable sources of discrepancy included variability in peripapillary atrophy seen on the photograph, and variability seen in the extent of the field. Reproducibility studies found a median absolute difference of 0.19 Macular Photocoagulation Study disc areas (DA) in total atrophy between repeat drawings, with 75% of repeat drawings having a difference of less than 0.33 DA. For central atrophy measures, there was a median difference of 0.08 DA, with 75% of pairs having a difference of less than 0.18 DA. Features making the definition of borders of GA difficult include the presence of drusen and pigmentary alteration, a fundus in which choroidal vessels are easily visible, and variation in the appearance of GA within a single area of atrophy. CONCLUSIONS: This method provides a reliable means of measuring the size of atrophic areas in GA and will be useful for measuring longitudinal change. It may be difficult to determine whether central spared areas are present, and correlation with visual acuity and macular perimetry may be helpful.

The natural history of geographic atrophy, the advanced atrophic form of age-related macular degeneration.

Geographic atrophy is the advanced form of atrophic age-related macular degeneration. It is present in 3.5% of people age 75 and over in the United States. It progresses gradually over time, often sparing the fovea until late in the course of the disease. Forty to fifty percent of eyes with geographic atrophy and good visual acuity at baseline lose three or more lines of acuity by two years and 27% become worse than 20/200 by four years. This article discusses the information known about age-related geographic atrophy at the present time.

Central serous chorioretinopathy and pregnancy.

BACKGROUND AND OBJECTIVE: Fourteen cases of central serous chorioretinopathy in pregnancy had been reported before this study was conducted. These cases have suggested a nonwhite predominance. Subretinal fibrinous exudates have been seen in 90% of the patients, compared with fewer than 20% of patients in typical (nonpregnant) central serous chorioretinopathy. No case has recurred outside of pregnancy, to our knowledge, and there have been no reports of subsequent pregnancies uninvolved by this disorder. These findings led us to collect our cases of central serous retinopathy in pregnancy because our experience differed from that of previous reports and provides additional new information. DESIGN: Case series. SETTING: The Wilmer Institute Retinal Vascular Center, Baltimore, Md. PATIENTS: Questionnaires sent to retinal faculty and fellows and a review of files revealed four patients, all included herein, with central serous chorioretinopathy presenting during pregnancy. RESULTS: All four patients were white. Three patients had subretinal fibrinous exudates and/or precipitates. All experienced resolution of the serous detachment near the end of the pregnancy or within the first few months after delivery. Only one patient had a subsequent pregnancy, and this was not complicated by the presence of central serous chorioretinopathy. One other patient experienced a recurrence 2 1/2 years after her last pregnancy. CONCLUSIONS: There may be no racial predominance in the development of central serous chorioretinopathy in pregnancy. Subretinal fibrinous exudates are quite common, independent of race. The uninvolved subsequent pregnancy suggests that recurrence in the context of pregnancy is not inevitable. This disorder may recur outside of pregnancy.

Retinal sensitivity over drusen and nondrusen areas. A study using fundus perimetry.

Elderly patients with drusen and good visual acuity have a decrease in dark-adapted retinal sensitivity in the central retina. We used the fundus camera stimulator to determine whether this sensitivity loss is caused directly by the presence of drusen. We measured retinal sensitivity over drusen and in drusen-free areas in eight patients with drusen and age-related macular degeneration (AMD). There was no significant difference in sensitivity between drusen and nondrusen areas in each patient. The sensitivity loss seen in patients with drusen thus seems to reflect a more diffuse disease of the retina and retinal pigment epithelium and is not a direct effect of drusen. More marked sensitivity losses are found in even small areas of more advanced AMD changes, suggesting that a large focal loss in retinal sensitivity may be an indicator of developing AMD changes.

Peripheral retinal function in age-related macular degeneration.

Aging changes are seen histopathologically outside the central retina, but have not been correlated with the presence of age-related macular degeneration (AMD). We studied 21 patients with drusen and AMD to see if peripheral retinal function changes are correlated with changes in the central retina. Electrooculogram Arden ratios were normal. Intensity-response analysis of dark-adapted electroretinogram b-waves and analysis of flicker electroretinograms were normal except for a small sensitivity loss presumed to reflect aging and lens yellowing. There was no difference between patients' severely involved AMD eye and their fellow eye with only drusen. Static perimetry showed sensitivity loss in the central 20 degrees, but normal thresholds peripheral to this. These results suggest that retinal function abnormalities in AMD are confined to the central retina, and the small age-related peripheral changes found do not correlate with the degree of AMD.

Retinal pigment epithelial tears through the fovea with preservation of good visual acuity.

We describe two patients with spontaneous retinal pigment epithelial tears through the fovea who have maintained at least 20/40 visual acuity for 1 year and 3 years following the rip. Both patients had long-standing serous detachments of the retinal pigment epithelium associated with age-related macular degeneration prior to the development of the tear. Each tear was at least five disc areas in size and centered on the fovea. Foveal fixation was documented despite the presumed absence of pigment epithelium. This observation suggests either that there may be remaining or redundant pigment epithelium or that pigment epithelium directly beneath the central macula is not required for maintenance of 20/40 visual acuity.

The pregnant woman's eye.

The effects of pregnancy on the eye fall into three categories. Nonpathological physiologic changes in pressures, corneal sensitivity and thickness, and visual function can occur. Pathologic conditions reported to develop during pregnancy include central serous chorioretinopathy, hypertensive and vascular disorders, and uveal melanoma. Pregnancy also can affect pre-existing ocular conditions, such as diabetic retinopathy, tumors, and a variety of immunological disorders and can have beneficial effects on such pre-existing conditions as glaucoma. This review covers ocular disorders in these three categories, and summarizes the systemic changes of pregnancy and the effects of ocular medications on the fetus.

Scanning laser ophthalmoscopic analysis of the pattern of visual loss in age-related geographic atrophy of the macula.

PURPOSE: We explored the clinical impression that geographic atrophy of the retinal pigment epithelium, a form of advanced age-related macular degeneration, is perceived by the patient as progressing gradually, even when fixation switches from foveal to extrafoveal. METHODS: We analyzed the responses of 60 patients with geographic atrophy to a questionnaire administered as part of a five-year study of the natural course of geographic atrophy, funded by the National Eye Institute. We performed scanning laser opthalmoscope perimetry on all patients. We examined two additional patients with geographic atrophy who reported abrupt visual loss. RESULTS: No eye with geographic atrophy was reported by any patient to have had sudden visual loss. Although most patients with geographic atrophy show foveal fixation until the fovea is atrophic and then show extrafoveal fixation, scanning laser ophthalmoscope perimetry in three patients with geographic atrophy showed alternation between a foveal and an extrafoveal retinal locus for fixation. Two patients with geographic atrophy who complained of abrupt visual loss were found to have occult choroidal neovascularization, which evolved in one patient to classic choroidal neovascularization. The neovascularization was difficult to detect because of the presence of geographic atrophy and its associated ophthalmoscopic and fluorescein angiographic features. CONCLUSIONS: Visual loss in geographic atrophy is nearly always perceived by the patient as being gradual, even when considerable decreases in visual acuity occur and when foveal vision and fixation are lost. A possible explanation for this perception is that there is a transitional period during which a patient uses both a foveal and extrafoveal site for fixation. The complaint of abrupt visual loss in a patient with geographic atrophy should raise the suspicion of choroidal neovascularization, which may be occult and difficult to detect.

Scanning laser ophthalmoscope fundus perimetry after surgery for choroidal neovascularization.

PURPOSE: Submacular surgery is under investigation for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration, ocular histoplasmosis syndrome, and other causes. The aims of this study were to determine whether the macular area from which choroidal neovascularization was removed surgically remained functional and whether there was any qualitative difference between eyes with different disease conditions or between eyes of younger and older patients. METHODS: Our study included 19 patients (19 eyes) with choroidal neovascularization, seven cases caused by age-related macular degeneration and 12 caused by ocular histoplasmosis syndrome, pathologic myopia, or idiopathic causes. All tests were performed at least 6 months after surgical removal of choroidal neovascularization. All patients underwent fundus perimetry with the scanning laser ophthalmoscope for evaluation of dense and relative scotomas and fixation site. RESULTS: After submacular surgery in 19 patients, 10 patients (one with age-related macular degeneration and nine with pathologic myopia, ocular histoplasmosis syndrome, or an idiopathic cause of choroidal neovascularization) fixated within an area that ophthalmoscopically and angiographically was an area of retinal pigment epithelial disturbance occupied by choroidal neovascularization preoperatively. Of 12 patients without age-related macular degeneration, seven of eight patients younger than 50 years of age compared with two of four patients 50 years or older fixated within the area of retinal pigment epithelial disturbance. CONCLUSIONS: Our data suggest that in patients without age-related macular degeneration who undergo submacular surgery, the surgically disturbed area previously occupied by choroidal neovascularization can remain functional postoperatively. Furthermore, occasionally a patient with age-related macular degeneration undergoing submacular surgery still can fixate in the area from which the choroidal neovascularization was removed.

A novel mutation in the ABCR gene in four patients with autosomal recessive Stargardt disease.

PURPOSE: To identify additional mutations in the ABCR gene and describe the clinical features of four affected siblings with autosomal recessive Stargardt disease. METHODS: A cohort of eight siblings was identified for study. Four of these individuals were diagnosed with Stargardt disease based on clinical evaluation and fluorescein angiography. Blood samples were obtained from seven of eight siblings, including all those affected. All 50 exons of the ABCR gene were analyzed by single-stranded confirmation polymorphism analysis, followed by direct sequencing of observed variants, to identify mutations in the ABCR gene. RESULTS: We identified a previously unreported kindred of eight siblings, four of whom had mutations in both of their ABCR alleles. A previously described G-to-C transversion of nucleotide 2588, predicting a Gly863Ala amino acid substitution, and a novel G-to-A transition of nucleotide 161, resulting in a Cys54Tyr substitution, were identified. These mutations co-segregated with the affected members of this family. Three of the siblings demonstrated clinical features characteristic of classic Stargardt disease, with bilateral regions of macular atrophy associated with yellow-white "flavimaculatus" flecks in the posterior pole at the level of the retinal pigment epithelium. The fourth affected sibling showed features of early Stargardt disease, with a beaten-bronze appearance to both maculas, as well as perimacular flecks. In all four affected patients, fluorescein angiography showed a characteristic peripheral dark choroid. CONCLUSIONS: We have identified both a previously described and a novel mutation in the ABCR gene in four patients with autosomal recessive Stargardt disease. In-depth knowledge of the ABCR mutation spectrum in patients with Stargardt disease will provide for more efficient screening and may provide potential therapies for Stargardt disease and other retinal diseases.

Docosahexaenoic acid therapy in peroxisomal diseases: results of a double-blind, randomized trial.

OBJECTIVES: Peroxisome assembly disorders are genetic disorders characterized by biochemical abnormalities, including low docosahexaenoic acid (DHA). The objective was to assess whether treatment with DHA supplementation would improve biochemical abnormalities, visual function, and growth in affected individuals. METHODS: This was a randomized, double-blind, placebo-controlled trial conducted at a single center. Treatment groups received supplements of DHA (100 mg/kg per day). The primary outcome measures were the change from baseline in the visual function and physical growth during the 1 year follow-up period. RESULTS: Fifty individuals were enrolled and randomized. Two were subsequently excluded from study analysis when it was determined that they had a single enzyme disorder of peroxisomal beta oxidation. Thirty-four returned for follow-up. Nine patients died during the trial of their disorder, and 5 others were lost to follow-up. DHA supplementation was well tolerated. There was no difference in the outcomes between the treated and untreated groups in biochemical function, electroretinogram, or growth. Improvements were seen in both groups in certain individuals. CONCLUSIONS: DHA supplementation did not improve the visual function or growth of treated individuals with peroxisome assembly disorders. CLASSIFICATION OF EVIDENCE: This interventional study provides Class II evidence that DHA supplementation did not improve the visual function or growth of treated individuals with peroxisome assembly disorders during an average of 1 year of follow-up in patients aged 1 to 144 months.

Focal electro-oculogram in age-related macular degeneration.

Age-related macular degeneration (AMD) is an important cause of vision loss among the elderly. Because patients with early subretinal neovascular membranes due to AMD can be treated by laser photocoagulation it becomes critical to find tests which can detect early changes. Inasmuch as AMD involves the retinal pigment epithelium, one might expect the electro-oculogram (EOG) to be sensitive to AMD pathology, but the ganzfeld EOG has been found to be normal in most cases. We designed a focal EOG apparatus to try to emphasize the contribution of the central retina, where AMD is found, to the EOG. Seventeen patients with various stages of drusen and AMD were tested and compared with normals. The focal EOG did not separate the AMD patients from the normals, nor did it give different distributions for the various subgroups of AMD. The focal EOG, like the ganzfeld EOG, is not a sensitive test for AMD.

Improvement of visual acuity over time in patients with bilateral geographic atrophy from age-related macular degeneration.

PURPOSE: To study the improvement in visual acuity over time in patients with central scotomas. METHODS: In a prospective natural history study of geographic atrophy (GA) from age-related macular degeneration (ARMD) with annual follow-up, 36 patients with bilateral GA completed 3 years of follow-up. Protocol visual acuity (VA) measurements were performed. Scanning laser ophthalmoscopy (SLO) was performed, and the areas of GA were measured from fundus photographs. RESULTS: Six eyes of six patients with VA ranging from 20/80 to 20/500 had a VA improvement of two or more lines (mean, 3.2 lines). This was found only in the worse-seeing eyes of the patients and was contemporaneous with the deterioration in VA of the better-seeing eyes. Four of six eyes that improved in acuity had an improvement in the ability to find and hold the fixation target in an area of seeing retina, as assessed by SLO at follow-up, and a fifth eye changed from one fixation site that had little functional retina to another site. CONCLUSIONS: Spontaneous improvement in VA in eyes with bilateral GA and central scotomas may occur. It appears to be related to deterioration in VA of the better-seeing fellow eye and is associated with improvement of fixation in the worse-seeing eye. The worse-seeing eye of a patient with bilateral ARMD may have the potential for better vision than measured VA indicates. This finding may have implications for the choice of patients in treatment trials, for interpretation of long-term results, and for planning and assessment of low vision intervention.

The development of choroidal neovascularization in eyes with the geographic atrophy form of age-related macular degeneration.

OBJECTIVE: To determine the rate of developing choroidal neovascularization (CNV) in eyes with geographic atrophy (GA) from age-related macular degeneration (AMD) and the characteristics of the CNV in these eyes. DESIGN: Prospective natural history study with cohort analysis. PARTICIPANTS: One hundred fifty-two patients with GA and no CNV by fluorescein angiography in at least 1 eye, with annual follow-up. MAIN OUTCOME MEASURES: The development of CNV. RESULTS: Thirteen eyes with GA developed CNV. For patients with bilateral GA and no CNV at baseline, 2% developed CNV by 2 years and 11% by 4 years. For patients with CNV in the fellow eye, 18% developed CNV in the study eye with GA by 2 years and 34% by 4 years. The eyes that developed CNV experienced more acuity loss than did the eyes with only GA. Within the fellow eye CNV group, those study eyes with GA that had less central atrophy (and better acuity) at baseline were more likely to develop CNV. The CNV developed at a peripheral border of GA in nine eyes, in the spared foveal region in two eyes, and in both center and border in one eye. No eye developed CNV in the area of atrophy itself. The appearance of CNV was evanescent in some cases and had a final appearance of an enlarged area of GA. Twelve other eyes had hemorrhages without definite evidence of CNV; three were thought to be suspicious for CNV and the remainder were thought to be hemorrhages that may be seen in elderly patients. CONCLUSION: An eye with GA whose fellow eye has CNV is at significant risk for the development of CNV in the GA eye. A patient with bilateral GA and no evidence of CNV is at relatively low risk for developing CNV. The CNV may be evanescent and may not be detected. Intraretinal hemorrhages unrelated to CNV are relatively common in this older population.

Flicker electroretinogram in retinitis pigmentosa.

Electroretinograms (ERGs) were recorded as a function of flicker frequency from 5 to 50 Hz for 14 retinitis pigmentosa (RP) patients, 12 normal subjects and 1 rod monochromat. Data were analyzed by measuring the angular position of the response maximum, i.e. the phase, as a function of pulse-train frequency. Flicker ERGs obtained from the RP patients showed non-linear, frequency-dependent phase shifts when compared to the normal data. These phase shifts were simulated in a normal observer by attenuating the stimulus luminance by 1 log unit. However, the shape of the waveforms recorded from the normal differed markedly from those recorded from the RP patients. The differences, but not the ratios of the times-to-peak of the positive and negative ERG wavelets were longer in the RP patients than in the normal. These data suggest that the temporal anomalies in the RP flicker ERG are most likely due to changes in the amplitudes and time constants of the ERG components, and not simply to a reduced quantum catch or photoreceptor loss.