Janet S. Sunness

Fixation patterns and reading rates in eyes with central scotomas from advanced atrophic age-related macular degeneration and Stargardt disease

PURPOSE To study fixation patterns and reading rates in eyes with central scotomas from geographic atrophy (GA) of age-related macular degeneration and to compare fixation patterns with those of patients with Stargardt disease. METHODS Scanning laser ophthalmoscope analysis of fixation patterns in eyes with 20/80 to 20/200 visual acuity. Included were 41 eyes of 35 patients with GA and 10 eyes of 5 patients with Stargardt disease. The patients with GA also were tested for maximum reading rate, and the size of the areas of atrophy were measured by fundus photograph analysis. RESULTS Sixty-three percent of GA eyes fixating outside the atrophy placed the scotoma to the right of fixation in visual field space, 22% placed the scotoma above fixation, and 15% placed it to the left, regardless of the laterality of the GA eye. Fixation was stable in subsequent years of testing for scotoma placement to the right of or above fixation. All GA eyes fixated immediately adjacent to the atrophy. In contrast, seven of ten eyes with Stargardt disease fixated at a considerable distance from the scotoma border, with the dense scotoma far above the fixation site in visual field space. For the patients with GA, the maximum reading rate was highly correlated with size of the atrophic area, but not with age or visual acuity within the limited visual acuity range tested. There was a trend to more rapid reading with the scotoma above fixation and slower reading with the scotoma to the left. CONCLUSION There is a preference for fixation with the scotoma to the right in eyes with GA. Patients with Stargardt disease use different strategies for fixation, perhaps due to subclinical pathology adjacent to the atrophic regions. The size of the atrophic area in GA plays the predominant role in reading rate for eyes that have already lost foveal vision.

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.

Visual Function Abnormalities and Prognosis in Eyes with Age-related Geographic Atrophy of the Macula and Good Visual Acuity

PURPOSE Geographic atrophy (GA) may cause significant compromise of visual function, even when there still is good visual acuity (VA), because of parafoveal scotomas and foveal function abnormalities antedating visible atrophy. This study evaluates the visual function abnormalities at baseline and the 2-year worsening of VA and reading rate for eyes with GA compared with a group of eyes with drusen only. METHODS Seventy-four eyes with GA and VA greater than or equal to 20/50 from a prospective natural history study of GA were included, as were 13 eyes with only drusen. Baseline visual function testing and 2-year VA and maximum reading rate are reported. RESULTS The worsening of VA in decreased luminance and foveal dark-adapted sensitivity showed severe abnormalities for the GA group. Contrast sensitivity was significantly reduced for the eyes with GA. Half the eyes with GA, but none of the drusen eyes, had maximum reading rates below 100 words per minute. A scanning laser ophthalmoscope (SLO) measure of the scotoma near fixation combined with a measure of residual foveal function accounted for 54% of the variability in maximum reading rate in the eyes with GA. Of 40 eyes with GA observed for 2 years, half lost greater than or equal to 3 lines of VA and one quarter lost greater than or equal to 6 lines. The nine eyes with drusen with follow-up had no significant change in VA. Low foveal dark-adapted sensitivity, SLO measures of the scotoma within 1 degree of fixation, and low maximum reading rate were statistically significant risk factors for doubling of the visual angle. Significant reduction in maximum reading rates at 2 years was present for the eyes with GA. CONCLUSIONS The eyes with GA with good VA have profound decreases in visual function, particularly in dim lighting and in reading. Half the eyes with GA had doubling in visual angle at 2 years after the baseline examination, whereas the drusen eyes remained essentially unchanged. Impaired visual function at baseline was predictive of an adverse outcome for the eyes with GA.

Patient selection for macular translocation surgery using the scanning laser ophthalmoscope

OBJECTIVES To evaluate the use of the scanning laser ophthalmoscope (SLO) as a predictor for potential visual improvement in eyes with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) undergoing limited macular translocation. DESIGN Retrospective noncomparative case series. PARTICIPANTS Consecutive series of 71 eyes of 70 patients with subfoveal CNV secondary to AMD that underwent effective and uncomplicated limited macular translocation at the Wilmer Ophthalmological Institute. METHODS Evaluation of the fundus microperimetry and fixation pattern was conducted on all patients using the Rodenstock scanning laser ophthalmoscope (G. Rodenstock Instrument GmbH, Munich, Germany) within 72 hours before surgery. MAIN OUTCOME MEASURES Sensitivity and specificity in addition to positive and negative predictive values of SLO findings for visual outcome after macular translocation. RESULTS Stable fixation presented the highest positive predictive value for visual acuity equal to or better than 20/100 (30 of 33 = 0.91), and predominantly eccentric fixation had the highest negative predictive value for visual acuity worse than 20/100 (7 of 9 = 0.78). Sensitivity was higher for the presence of predominantly central fixation (42 of 48 = 0.87), and specificity was higher for relatively unstable/unstable fixation (20 of 23 = 0.87). CONCLUSIONS Eyes with stable and central fixation (without dense central scotoma) good preoperative visual acuity, and short length of symptoms are those with the greatest chance to achieve good vision after macular translocation. The knowledge of the fixation and microperimetry pattern enables better understanding of the macular function in eyes with AMD and may be useful for evaluation of baseline retinal cell viability. Incorporation of these testing modalities may help to optimize patient selection for macular translocation or other future techniques aimed at rescuing photoreceptors.

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.

Allogenic fetal retinal pigment epithelial cell transplant in a patient with geographic atrophy.

PURPOSE To test the hypothesis that healthy fetal retinal pigment epithelium (RPE) can rescue the remaining viable RPE and choriocapillaries and thereby the photoreceptors in non-neovascular age-related macular degeneration (ARMD) (geographic atrophy [GA]). METHODS A 65-year-old legally blind woman with non-neovascular ARMD underwent fetal RPE transplantation. Best-corrected visual acuity testing, detailed fundus examination, fundus photography, fluorescein angiography, scanning laser ophthalmoscope macular perimetry, and humoral and cellular immune response testing were performed. A suspension of RPE was infused into the subretinal space through a retinotomy along the superotemporal arcade at the edge of the area of GA. The patient did not take systemic immunosuppressants. RESULTS The patients vision remained unchanged for 5 months after the surgery. Fluorescein angiography after transplantation showed leakage and staining at the level of the outer retina. There was progressive subretinal fibrosis in the area of the transplant. Immune response studies showed a weakly positive mixed lymphocyte response against phosducin and rhodopsin. CONCLUSION Although it is surgically feasible to transplant fetal RPE to the subretinal space of patients with GA, such an allogenic RPE transplant without immunosuppression leads to leakage on fluorescein angiography and eventual fibrosis. A very weak immune response against proteins associated with photoreceptors is also of concern.

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.

Diminished foveal sensitivity may predict the development of advanced age-related macular degeneration

Visual function testing was performed on one eye with drusen from each of 18 elderly patients in 1984. Eleven patients had advanced age-related macular degeneration (AMD) in the fellow eye, and seven had only bilateral drusen. These patients were all followed prospectively (median, 45 months), at which time one eye had a new vessel membrane, three eyes had pigment epithelial detachments, and one eye had geographic atrophy. Only two of these five eyes had AMD-related visual loss in the fellow eye in 1984. The degree of loss of foveal dark-adapted sensitivity in 1984 predicted which patients developed advanced AMD with 100% sensitivity and 92% specificity. The presence of high-risk drusen characteristics in 1984 predicted the development of advanced AMD with 100% sensitivity but only 55% specificity. For this small group of patients, foveal dark-adapted sensitivity loss was an excellent predictor of the subsequent development of advanced AMD in eyes with drusen. A prospective study of a large group of patients with drusen is being undertaken to validate this finding.

Characteristics of visual loss by scanning laser ophthalmoscope microperimetry in eyes with subfoveal choroidal neovascularization secondary to age-related macular degeneration.

PURPOSE To evaluate the effects of subfoveal choroidal neovascularization secondary to age-related macular degeneration on functional parameters obtained by scanning laser ophthalmoscope microperimetry. DESIGN Retrospective observational case series and cross-sectional study. METHODS At the Doheny Retina Institute and Wilmer Eye Institute a consecutive series of 179 eyes of 175 patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration was studied. The onset of visual symptoms, best-corrected visual acuity, fluorescein angiography, evaluation of fundus microperimetry and fixation pattern using the Rodenstock scanning laser ophthalmoscope were obtained for each patient. The main outcome measures were central retinal sensitivity and fixation pattern (fixation location and fixation stability) in eyes with subfoveal choroidal neovascularization and their relationship to the length of disease, type and characteristics of choroidal neovascularization, and visual acuity. RESULTS Of 179 eyes, 135 (75%) had central fixation, 27 (15%) had poor central fixation, and 17 (9%) had predominantly eccentric fixation. Seventy-six eyes (42%) had stable fixation, 70 eyes (39%) had relatively unstable fixation, and 33 eyes (18%) had unstable fixation. In 50 eyes (28%) a dense central scotoma was noted. Eighty-nine of 100 eyes (89%) with length of symptoms of less than 3 months had predominantly central fixation and 58 (58%) had stable fixation; 14 of 34 eyes (41%) with length of symptoms of more than 6 months had predominantly central fixation, and 5 eyes (15%) had stable fixation. In 15 eyes of patients who elected not to receive treatment, successive scanning laser ophthalmoscope microperimetry were obtained over time (follow-up of 18 months after onset of symptoms). Three months or less after the onset of symptoms, 13 eyes (87.7%) had predominantly central fixation and 9 eyes (60%) had stable fixation. More than 3 months and 6 months or less after the onset of symptoms, 10 eyes (66.7%) had predominantly central fixation and 7 eyes (46.7%) had stable fixation. This trend was further demonstrated in eyes more than 6 months after the onset of symptoms. CONCLUSIONS We conclude that the sequence of events leading to visual function deterioration appears to involve an initial mild decrease in central retinal sensitivity and visual acuity followed by progressive fixation instability and, ultimately, development of an absolute central scotoma with totally eccentric fixation. Increased length of disease is associated with worse fixation pattern and retinal sensitivity deterioration as assessed by scanning laser ophthalmoscope microperimetry. A better understanding of the characteristics of visual loss assessed by fixation pattern evaluation and microperimetry in age-related macular degeneration may help optimize timing, patient selection, and treatment options in eyes with this condition.

Redefining papillorenal syndrome: an underdiagnosed cause of ocular and renal morbidity.

PURPOSE To report ocular and renal findings specific to the inheritable entity called papillorenal (also known as renal-coloboma) syndrome and relate these to a common cause. DESIGN Observational case series and genetic study. PARTICIPANTS Two unrelated probands presenting with absent central retinal vessels and 11 available family members. TESTING Doppler ultrasonographic imaging of the optic nerves and kidneys, fluorescein angiography, and genetic testing for PAX2 mutations were performed. In selected cases, indocyanine green angiography, scanning laser ophthalmoscope perimetry, Retinal Thickness Analyzer measurements, visual evoked potentials, and magnetic resonance imaging were also performed. MAIN OUTCOME MEASURES Better defined characteristics of the papillorenal syndrome. RESULTS Numerous cilioretinal vessels were present with rudimentary or absent central retinal vessels. Superonasal visual field defects, typical for papillorenal syndrome, corresponded to inferotemporal areas of anomalous retinal and choroidal perfusion and hypoplastic retina. Renal hypoplasia was discovered in two affected members of one family (with previously unsuspected renal failure in one case), and recurrent pyelonephritis was discovered in four affected members of the other family. No PAX2 mutations were detected. CONCLUSIONS In the papillorenal syndrome, the hereditary absence of central retinal vessels may be missed, leading to confusion with isolated coloboma, low-tension glaucoma, and morning glory anomaly. Greater awareness of this syndrome will avoid unneeded glaucoma therapy, allow earlier recognition of renal diseases, and allow genetic counseling. We propose that the papillorenal syndrome is a primary dysgenesis that causes vascular abnormalities predominantly affecting the eye, kidney, and urinary tract, leading to hypoplasia of these structures. The absence of defects in the PAX2 gene in these families suggests that mutations in other genes may also be responsible for this syndrome.