Faculty Bibliography

PURPOSE: To report the presence of a hyperautofluorescent ring and corresponding spectral-domain optical coherence tomography (SD-OCT) features seen in patients with autoimmune retinopathy. METHODS: All eyes were evaluated by funduscopic examination, full-field electroretinography, fundus autofluorescence, and SD-OCT. Further confirmation of the diagnosis was obtained with immunoblot and immunohistochemistry testing of the patient's serum. Humphrey visual fields and microperimetry were also performed. RESULTS: Funduscopic examination showed atrophic retinal pigment epithelium (RPE) associated with retinal artery narrowing but without pigment deposits. The scotopic and photopic full-field electroretinograms were nondetectable in three patients and showed a cone-rod pattern of dysfunction in one patient. Fundus autofluorescence revealed a hyperautofluorescent ring in the parafoveal region, and the corresponding SD-OCT demonstrated loss of the photoreceptor inner segment-outer segment junction with thinning of the outer nuclear layer from the region of the hyperautofluorescent ring toward the retinal periphery. The retinal layers were generally intact within the hyperautofluorescent ring, although the inner segment-outer segment junction was disrupted, and the outer nuclear layer and photoreceptor outer segment layer were thinned. CONCLUSION: This case series revealed the structure of the hyperautofluorescent ring in autoimmune retinopathy using SD-OCT. Fundus autofluorescence and SD-OCT may aid in the diagnosis of autoimmune retinopathy and may serve as a tool to monitor its progression

PURPOSE: To compare MP-1 microperimeter and Humphrey Field Analyzer (HFA) defects, in patients with retinitis pigmentosa (RP), a disease primarily affecting the photoreceptors, and in patients with glaucoma, a disease primarily affecting postreceptoral ganglion cells, and to analyze the similarities and differences between the results. METHODS: Eleven patients (11 eyes) with RP and 10 patients (10 eyes) with primary open-angle glaucoma (OAG) underwent MP-1 and HFA visual field testing (10-2 pattern). All tested eyes had defects encroaching within 10 degrees of fixation. MP-1 total deviation (TD) probability defects, derived from a previously collected normative database of 50 subjects, were compared to HFA TD defects and to the local defect map of the MP-1. Test duration was compared between instruments. RESULTS: In RP patients, MP-1 scotomata were deeper and wider than HFA defects; however in OAG, the opposite was observed. Examination duration in both patient groups was 12 to 14 min for the MP-1 and 6 min for the HFA. The MP-1 local defect map tended to overestimate defects compared to the MP-1 TD analysis. CONCLUSIONS: The differences in results between the MP-1 and HFA for the two groups of patients with RP and OAG can be attributed to the different adaptation levels and to the dynamic range of test lights available for the two instruments. The clinician should also be aware of the possible consequences of the differences in the method of derivation of normative data for the two instruments, as this may affect the interpretation of visual field results.

PURPOSE: To evaluate the constriction of the hyperautofluorescent ring over time in patients with retinitis pigmentosa (RP). DESIGN: Prospective study. METHODS: Fourteen eyes of 14 RP patients with a hyperautofluorescent ring were studied. Ring constriction was evaluated by measurements of its external and internal boundaries along the vertical and horizontal axes at baseline and at 12-, 24-, 36-, and 48-month follow-ups. Repeat fundus autofluorescence was obtained at 12, 24, 36, and 48 months in 13, 7, 5, and 1 eyes respectively. Spectral-domain optical coherence tomography (SD-OCT) images were obtained on 8 eyes and the horizontal extent of the inner segment/outer segment (IS/OS) junction was measured. SD-OCT was repeated at 12 and 24 months in 6 and 4 eyes respectively. RESULTS: The external boundaries of the ring were identified along the horizontal axis in 12 eyes and along the vertical axis in 13. Internal boundaries were identified in 7 eyes. Constriction was demonstrated in all patients except 1 who demonstrated minimal expansion of the internal boundary along the horizontal axis. SD-OCT measurements showed a decrease in the IS/OS junction length. CONCLUSION: Progressive constriction of the hyperautofluorescent ring and a concordant decrease in IS/OS junction length were observed over time

PURPOSE:: To analyze the structure and visual function of regions bordering the hyperautofluorescent ring/arcs in retinitis pigmentosa. METHODS:: Twenty-one retinitis pigmentosa patients (21 eyes) with rings/arcs and 21 normal individuals (21 eyes) were studied. Visual sensitivity in the central 10 degrees was measured with microperimetry. Retinal structure was evaluated with spectral-domain optical coherence tomography. The distance from the fovea to disruption/loss of the inner outer segment (IS/OS) junction and thicknesses of the total receptor plus retinal pigment epithelial complex and outer segment plus retinal pigment epithelial complex layers were measured. Results were compared with measurements of the distance from the fovea to the inner and outer borders of the ring/arc seen on fundus autofluorescence. RESULTS:: Disruption/loss of the inner outer segment junction occurred closer to the inner border of the ring/arc and it was closer to the fovea in eight eyes. For 19 eyes, outer segment plus and receptor plus RPE complex thicknesses were significantly decreased at locations closer to the fovea than the appearance of the inner border of hyperautofluorescence. Mean visual sensitivity was decreased inside, across, and outside the ring/arc by 3.5 +/- 3.8, 8.9 +/- 4.8, and 17.0 +/- 2.4 dB, respectively. CONCLUSION:: Structural and functional changes can occur inside the hyperfluorescent ring/arc in retinitis pigmentosa

Purpose. To describe the structural changes across the transition zone (TZ) in choroideremia (CHM) and Stargardt disease (STGD) and to compare these to the TZ in retinitis pigmentosa (RP). Methods. Frequency-domain (Fd)OCT line scans were obtained from seven patients with CHM, 20 with STGD, and 12 with RP and compared with those of 30 previously studied controls. A computer-aided manual segmentation procedure was used to determine the thicknesses of the outer segment (OS) layer, the outer nuclear layer plus outer plexiform layer (ONL+), the retinal pigment epithelium plus Bruch's membrane (RPE+BM), and the outer retina (OR). Results. The TZ, while consistent within patient groups, showed differences across disease groups. In particular, (1) OS loss occurred before ONL+ loss in CHM and RP, whereas ONL+ loss occurred before OS loss in STGD; (2) ONL+ was preserved over a wider region of the retina in CHM than in RP; (3) RPE+BM remained normal across the RP TZ, but was typically thinned in CHM. In some CHM patients, it was abnormally thin in regions with normal OS and ONL+ thickness. In STGD, RPE+BM was thinned by the end of the TZ; and (4) the disappearances of the IS/OS and OLM were more abrupt in CHM and STGD than in RP. Conclusions. On fdOCT scans, patients with RP, CHM, and STGD all have a TZ between relatively healthy and severely affected retina. The patterns of changes in the receptor layers are similar within a disease category, but different across categories. The findings suggest that the pattern of progression of each disease is distinct and may offer clues for strategies in the development of future therapies

To evaluate eyes with abnormal visual fields and multifocal electroretinograms (mfERGs) but normal-appearing frequency-domain optical coherence tomography (fdOCT) scans, the thicknesses of the outer retinal layers were measured. A total of 25 eyes from 17 patients, including 15 eyes previously tested (Dale et al. in Doc Ophthalmol 120(2):175-186, 2009) were examined. All patients were evaluated with standard automated perimetry (SAP) using the 24-2 and/or 10-2 program (Zeiss Meditec), mfERG with 103 hexagons (Veris, EDI), and fdOCT imaging (3DOCT-2000, Topcon) with scans of the macula. All patients had reliable visual fields showing macular defects and good quality mfERG and fdOCT results. The mfERG results were classified as abnormal based on decreased amplitudes and/or increased latencies corresponding to the abnormal visual field. Based on visual inspection, three experienced observers classified the fdOCT scans as normal or inconclusive, as opposed to clearly abnormal. Retinal layers of the fdOCT scans were manually segmented with the aid of a computer program and compared to mean thicknesses from 20 controls. The thicknesses of the outer segment plus retinal pigment epithelium, total receptor, and inner nuclear layers were measured. Quantitative analysis of fdOCT scans demonstrated thinning of the outer retina in some scans that was not readily apparent on visual inspection. One or more of the outer retinal layers was significantly thinner in 15 of the 25 eyes. The absence of significant thinning in the other 10 eyes represents instances in which functional loss measured by visual fields and mfERGs can precede clear structural changes on fdOCT

PURPOSE: To compare visual fields on the Nidek MP-1 to those obtained on the Humphrey field analyzer (HFA) in healthy volunteers and assess the effects of differences in stimulus parameters and testing strategies that may influence the interpretation of results in patients. A secondary aim was to establish MP-1 normative data to calculate the total deviation analyses and global indices analogous to those used by the HFA. METHODS: Fifty healthy volunteers (age 43.5 +/- 13.9 years, range, 18 to 68 years) underwent repeat MP-1 and HFA visual field testing, using the 10-2 pattern. MP-1 data were converted to HFA equivalent dB units. Between instrument comparisons of HFA and MP-1 sensitivities, regression of sensitivity with age and examination duration were assessed. Test-retest variability was examined between visits. RESULTS: MP-1 (mean = 32.82 dB, SD = 1.92 dB) and HFA sensitivities (mean = 32.84 dB, SD = 1.83 dB) were not significantly different (p = 0.759). SD values for the HFA (range, 1.11 to 3.30 dB) were similar to the MP-1 (range, 0.14 to 2.75 dB). However, asymmetry comparisons between instruments showed significantly decreased superior rather than inferior retinal values for the MP-1. There was a small but significant difference (p = 0.004) in mean test duration between the MP-1 (mean = 6:11 min, SD = 1:49 min) and the HFA (mean = 5:14 min, SD = 0:42 min). There was also a difference in the decline of mean sensitivity with age, a decline of 0.1 and 0.4 dB per decade was noted in MP-1 and HFA sensitivity, respectively. Test-retest variability was similar between instruments. A small but non-significant increase in mean sensitivity at the second visit for both the MP-1 (p = 0.060) and HFA (p = 0.570) was found. CONCLUSIONS: Both instruments showed similar variability and test-retest variability when results were compared using equivalent units. However, there are important differences in sensitivity values, stimulus parameters, and testing strategies that have to be taken into account when comparisons are made

PURPOSE: To quantify and compare structure and function across the macula and peripapillary area in Stargardt disease (STGD1). METHODS: Twenty-seven patients (27 eyes) and 12 age-similar controls (12 eyes) were studied. Patients were classified on the basis of full-field electroretinogram (ERG) results: Fundus autofluorescence (FAF) and spectral domain-optical coherence tomography (SD-OCT) horizontal line scans were obtained through the fovea and peripapillary area. The thicknesses of the outer nuclear layer plus outer plexiform layer (ONL+), outer segment (OS), and retinal pigment epithelium (RPE) were measured through the fovea, and peripapillary areas from 1 degrees to 4 degrees temporal to the optic disc edge using a computer-aided, manual segmentation technique. Visual sensitivities in the central 10 degrees were assessed using microperimetry and related to retinal layer thicknesses. RESULTS: Compared to the central macula, the differences between controls and patients in ONL+, OS, and RPE layer thicknesses were less in the nasal and temporal macula. Relative sparing of the ONL+ and/or OS layers was detected in the nasal (i.e., peripapillary) macula in 8 of 13 patients with extramacular disease on FAF; relative functional sparing was also detected in this subgroup. All 14 patients with disease confined to the central macula, as detected on FAF, showed ONL+ and OS layer thinning in regions of normal RPE thickness. CONCLUSIONS: Relative peripapillary sparing was detected in STGD1 patients with extramacular disease on FAF. Photoreceptor thinning may precede RPE degeneration in STGD1

PURPOSE: To better understand hypodense regions (holes) that appear in the retinal nerve fiber layer (RNFL) of frequency-domain optical coherence tomography (fdOCT) scans of patients with glaucoma and glaucoma suspects. METHODS: Peripapillary circle (1.7-mm radius) and cube optic disc fdOCT scans were obtained on 208 eyes from 110 patients (57.4 +/- 13.2 years) with glaucomatous optic neuropathy (GON) and 45 eyes of 45 controls (48.0 +/- 12.6 years) with normal results of fundus examination. Holes in the RNFL were identified independently by two observers on the circle scans. RESULTS: Holes were found in 33 (16%) eyes of 28 (25%) patients; they were not found in any of the control eyes. Twenty-four eyes had more than one hole. Although some holes were relatively large, others were small. In general, the holes were located adjacent to blood vessels; only three eyes had isolated holes that were not adjacent to a vessel. The holes tended to be in the regions that are thickest in healthy controls and were associated with arcuate defects in patients. Holes were not seen in the center of the temporal disc region. They were more common in the superior (25 eyes) than in the inferior (15 eyes) disc. Of the 30 eyes with holes with reliable visual fields, seven were glaucoma suspect eyes with normal visual fields. CONCLUSIONS: The holes in the RNFL seen in patients with GON were probably due to a local loss of RNFL fibers and can occur in the eyes of glaucoma suspects with normal visual fields

The location of the loss of the inner segment (IS)/outer segment (OS) border, as seen with frequency domain optical coherence tomography (fdOCT), was determined on fdOCT scans from patients with retinitis pigmentosa. A comparison to visual field loss supported the hypothesis, based upon previous work, that the point at which the IS/OS border disappears provides a structural marker for the edge of the visual field. Repeat fdOCT measures showed good within day reproducibility, while data obtained on average 22.5 months later showed signs of progression. The IS/OS contour shows promise as a measure for following changes in patients undergoing treatment