Toward a Real-world Optical Coherence Tomography Reference Database: Optometric Practices as a Source of Healthy Eyes.

SIGNIFICANCE: The reports from optical coherence tomography (OCT) instruments depend on a reference database (RDB) of healthy eyes. Although these RDBs tend to be relatively small, they are time consuming and expensive to obtain. A larger RDB should improve our ability to screen for diseases such as glaucoma. PURPOSE: To explore the feasibility of developing a large RDB from OCT scans obtained by optometrists as part of their pre-test gathering of information, we tested the hypothesis that these scans are of sufficient quality for an RDB and contain a relatively low base rate of glaucoma and other pathologies (OPs). METHODS: Optical coherence tomography widefield (12 × 9 mm) scans from 400 eyes of 400 patients were randomly selected from a data set of more than 49,000 scans obtained from four optometry sites. Based on a commercial OCT report and a previously validated reading center method, two OCT graders categorized eyes as unacceptable to use for RDB, healthy (H), optic neuropathy consistent with glaucoma (ON-G), glaucoma suspect, or OPs. RESULTS: Overall, 29 (7.25%) of the eyes were graded unacceptable. Of the remaining 371 eyes, 352 (94.9%) were graded H. Although, for one site, 7.4% of the eligible eyes were graded ON-G, the average for the other three sites was 1.4%. Adjustments of the reading center criteria resulted in exclusion of more than half of these ON-G and OP eyes. CONCLUSIONS: The OCT scans obtained from optometry practices as part of their pre-test regimen are of sufficient quality for an RDB and contain a relatively low base rate of glaucoma and OPs. With the suggested exclusion criteria, the scans from optometry practices that are primarily involved in refraction and medical screening services should yield a large, real-world RDB with improved specificity and a base rate of glaucoma and/or OPs comparable with existing RDB.

Structure-function analysis for macular surgery in patients with coexisting glaucoma.

PURPOSE: To develop methods to assess the effects of epiretinal membranes (ERM) and macular holes (MH) coexisting with glaucoma on pre-operative retinal structure and function and evaluate post-operative outcomes. METHODS: Seven eyes of 7 patients with glaucoma, 6 with ERMs and 1 with MH, were enrolled; 4 underwent vitrectomy for ERM and one for MH. Visual fields (VFs) and optical coherence tomography (OCT) scans were obtained pre- and post-operatively. The 10-2VF deviation map was overlayed on ganglion cell and inner plexiform layer (GCL + IPL) and retinal nerve fiber layer (RNFL) deviation maps derived from OCT macula and disc cube scans. Optic nerve circle scans were obtained to assess RNFL thickness, and OCT b-scans associated with VF defects were compared pre- and post-operatively. RESULTS: Examination of pre-operative VFs and OCT scans showed the importance of determining the extent to which glaucomatous damage contributed to VF loss; verifying automated segmentation of the GCL + IPL and RNFL; and assessing foveal anatomy. Evaluation of post-operative structure-function outcomes required correction of magnification changes in OCT scans and repeated follow-up visits to clarify the origin of VF changes. CONCLUSIONS: Pre-operative comparisons of VFs and OCT scans may be beneficial in guiding surgical planning, and evaluating outcomes, in eyes with glaucoma undergoing macular surgery.

Detecting Progression in Advanced Glaucoma: Are Optical Coherence Tomography Global Metrics Viable Measures?

SIGNIFICANCE: Optical coherence tomography (OCT) summary measures have been suggested as a way to detect progression in eyes with advanced glaucoma. Here, we show that these measures have serious flaws largely due to segmentation errors. However, inspection of the images and thickness maps can be clinically useful. PURPOSE: This study aimed to test the hypothesis that recently suggested global OCT measures for detecting progression in eyes with advanced progression are seriously affected by segmentation mistakes and other errors that limit their clinical utility. METHODS: Forty-five eyes of 38 patients with a 24-2 mean deviation worse than -12 dB had at least two spectral domain OCT sessions (0.8 to 4.4 years apart) with 3.5-mm circle scans of the disc and cube scans centered on the fovea. Average (global) circumpapillary retinal nerve fiber layer thickness, GcRNFL, and ganglion cell plus inner plexiform layer thickness, GGCLP, were obtained from the circle and cube scan, respectively. To evaluate progression, ΔGcRNFL was calculated for each eye as the GcRNFL value at time 2 minus the value at time 1, and ΔGGCLP was calculated in a similar manner. The b-scans of the six eyes with the highest and lowest ΔGcRNFL and ΔGGCLP values were examined for progression as well as segmentation, alignment, and centering errors. RESULTS: Progression was a major factor in only 7 of the 12 eyes with the most negative values of either ΔGcRNFL or ΔGGCLP, whereas segmentation played a role in 8 eyes and was the major factor in all 12 eyes with the largest positive values. In addition, alignment (one eye) and other (three eyes) errors played a secondary role in four of the six eyes with the most negative ΔGcRNFL values. CONCLUSIONS: For detecting the progression of advanced glaucoma, common summary metrics have serious flaws largely due to segmentation errors, which limit their utility in clinical and research settings.

ACUTE ZONAL OCCULT OUTER RETINOPATHY: Structural and Functional Analysis Across the Transition Zone Between Healthy and Diseased Retina.

PURPOSE: To assess structure and function across the transition zone (TZ) between relatively healthy and diseased retina in acute zonal occult outer retinopathy. METHODS: Six patients (6 eyes; age 22-71 years) with acute zonal occult outer retinopathy were studied. Spectral-domain optical coherence tomography, fundus autofluorescence, near-infrared reflectance, color fundus photography, and fundus perimetry were performed and images were registered to each other. The retinal layers of the spectral-domain optical coherence tomography scans were segmented and the thicknesses of two outer retinal layers, that is, the total receptor and outer segment plus layers, and the retinal nerve fiber layer were measured. RESULTS: All eyes showed a TZ on multimodal imaging. On spectral-domain optical coherence tomography, the TZ was in the nasal retina at varying distances from the fovea. For all eyes, it was associated with loss of the ellipsoid zone band, significant thinning of the two outer retinal layers, and in three eyes with thickening of the retinal nerve fiber layer. On fundus autofluorescence, all eyes had a clearly demarcated peripapillary area of abnormal fundus autofluorescence delimited by a border of high autofluorescence; the latter was associated with loss of the ellipsoid zone band and with a change from relatively normal to markedly decreased or nonrecordable visual sensitivity on fundus perimetry. CONCLUSION: The results of multimodal imaging clarified the TZ in acute zonal occult outer retinopathy. The TZ was outlined by a distinct high autofluorescence border that correlated with loss of the ellipsoid zone band on spectral-domain optical coherence tomography. However, in fundus areas that seemed healthy on fundus autofluorescence, thinning of the outer retinal layers and thickening of the retinal nerve fiber layer were observed near the TZ. The TZ was also characterized by a decrease in visual sensitivity.

24-2 Visual Fields Miss Central Defects Shown on 10-2 Tests in Glaucoma Suspects, Ocular Hypertensives, and Early Glaucoma.

PURPOSE: To investigate the prevalence of visual field defects in glaucomatous eyes, glaucoma suspects, and ocular hypertensives with 24-2 and 10-2 visual fields. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Patients with or suspected glaucoma tested with 24-2 and 10-2. Patients were classified into 3 groups on the basis of the presence of glaucomatous optic neuropathy (GON) and 24-2 visual field abnormalities: early glaucoma (GON and abnormal visual field, mean deviation >-6 decibels [dB]), glaucoma suspects (GON and normal visual field), and ocular hypertensives (normal disc, normal visual field, and intraocular pressure >22 mmHg). For the classification of visual field abnormalities, 24-2 and 10-2 tests performed on the same visit were analyzed. MAIN OUTCOME MEASURES: Comparison of the prevalence of abnormal 24-2 versus 10-2 visual field results based on cluster criteria in each diagnostic group. RESULTS: A total of 775 eyes (497 patients) were evaluated. A total of 364 eyes had early glaucoma, 303 eyes were glaucoma suspects, and 108 eyes were ocular hypertensives. In the glaucoma group, 16 of the 26 eyes (61.5%) classified as normal based on cluster criteria on 24-2 tests were classified as abnormal on 10-2 visual fields. In eyes with suspected glaucoma, 79 of the 200 eyes (39.5%) classified as normal on the 24-2 test were classified as abnormal on 10-2 visual fields. In ocular hypertensive eyes, 28 of the 79 eyes (35.4%) classified as normal on the 24-2 were classified as abnormal on the 10-2. Patients of African descent were more likely to have an abnormal 10-2 result (67.3 vs. 56.8%, P = 0.009). CONCLUSIONS: Central visual field damage seen on the 10-2 test is often missed with the 24-2 strategy in all groups. This finding has implications for the diagnosis of glaucoma and classification of severity.

Cobalt-Chromium Metallosis With Normal Electroretinogram.

BACKGROUND: Ocular cobalt toxicity is a rare phenomenon reported with increased frequency due to the rise of cobalt-chromium metal hip implants. We report the case of a 66-year-old previously healthy man who developed decreased vision due to cobalt-chromium toxicity from a metal-on-metal hip arthroplasty. Our objective was to determine whether the origin of his visual loss was due to toxicity of the optic nerve, of the retina, or of both. METHODS: Ocular examination, 10-2 SITA-Standard Humphrey Visual Field (VF), standard full-field electroretinogram (ERG) as indicated by the International Society for Clinical Electrophysiology of Vision (ISCEV), multifocal electroretinogram (mfERG), multifocal visual evoked potentials (mfVEP), and optical coherence tomography (OCT) were conducted. RESULTS: Ocular examination revealed decreased visual acuity, poor color vision, normal funduscopy, and cecocentral scotomas on VF testing. Because his right eye was amblyopic since childhood, test results from only the left eye are shown. Electrophysiology studies revealed an ISCEV standard full-field ERG with photopic and scotopic responses within normal limits, mfERG with amplitudes and latencies within normal limits, and mfVEP with latencies within normal limits, but with decreased central amplitudes. Peripapillary and macular OCT showed retinal nerve fiber layer and retinal ganglion cell-inner plexiform layer thickness within normal limits. CONCLUSION: Because decreased color vision and cecocentral scotoma on 10-2 VF are most consistent with toxic optic neuropathy, and decreased central amplitudes on mfVEP are suggestive of neural dysfunction, we hypothesize that our patient presented with an early stage of optic nerve toxicity that was not yet apparent as a structural abnormality on OCT.

Rates of decline in regions of the visual field defined by frequency-domain optical coherence tomography in patients with RPGR-mediated X-linked retinitis pigmentosa.

PURPOSE: To determine whether annual decline in visual field sensitivity is greater in the transition zone at the edge of the frequency-domain optical coherence tomography (fdOCT) inner segment ellipsoid zone (EZ) than at other locations in the visual field. DESIGN: Prospective, longitudinal, observational study. PARTICIPANTS: Forty-four patients with X-linked retinitis pigmentosa (XLRP) resulting from a mutation in the RPGR gene. METHODS: Static perimetric fields (Humphrey 30-2; Carl Zeiss Meditec, Dublin, CA) were obtained annually for 4 years. Beginning with year 2, fdOCT scans were obtained annually with a Heidelberg Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany). MAIN OUTCOME MEASURES: The rate of visual field decline at locations near the edge of the EZ compared with the rates for the macula and in the mid periphery. RESULTS: Sensitivity just inside and outside the edge of the EZ declined at rates of 0.84 and 0.92 dB/year, respectively. By comparison, average sensitivity in the macula and mid periphery declined by 0.38 and 0.61 dB/year, respectively. CONCLUSIONS: The edge of the EZ in each patient with XLRP indicates a transition zone between relatively healthy and relatively degenerate retina. The annual loss of sensitivity in the transition zone is more rapid than it is elsewhere in the retina.

A comparison of structural and functional changes in patients screened for hydroxychloroquine retinopathy.

PURPOSE: The aims of this retrospective study were to compare the results of recommended screening tests for hydroxychloroquine-related retinal toxicity and analyze disparities between the structural and functional findings. METHODS: Thirty-four patients (31 women and 3 men) were included in the study. All were evaluated with standard automated perimetry using the 10-2 and/or 24-2 visual field program (Zeiss, Meditec), multifocal electroretinography (mfERG), spectral-domain optical coherence tomography (SD-OCT), and short-wavelength fundus autofluorescent imaging (SW-FAF). The results for the right eye from each patient were analyzed. Visual fields were classified as normal or abnormal based on pattern deviation plots, and mfERGs based on a comparison of R5 ring ratios to values from 20 controls. The SW-FAF images were examined for areas/rings of abnormal hypo- and/or hyperautofluorescence, and the SD-OCT line scans were classified as abnormal based on visual inspection and thickness measurements of the outer segment plus retinal pigment epithelial layer and total receptor layers compared to mean thicknesses from 35 controls. RESULTS: Fifteen patients had abnormal results on at least one test; however, only two patients had abnormal results on all four tests. Excluding SW-FAF, seven of the 15 had abnormal visual fields, mfERG ring ratios, and SD-OCTs. The remaining eight had either abnormal mfERGs and/or visual fields and normal SD-OCTs. We found no evidence of abnormal SD-OCTs in the presence of normal mfERG and visual field results. CONCLUSIONS: The findings suggest that functional deficits precede structural changes seen on SD-OCT in these patients.

Glaucoma Detection Using Optical Coherence Tomography: Reviewing the Pitfalls of Comparison to Normative Data.

PRCIS: Optical coherence tomography is essential in managing glaucoma. This review describes various artifacts that originate from using a normative database to compare the individual's scans. This is a review paper regarding artifacts in optical coherence tomography imaging for glaucoma arising from using a normative database as a reference for healthy retinal nerve fiber layer and ganglion cell layer.

Anatomical Features can Affect OCT Measures Used for Clinical Decisions and Clinical Trial Endpoints.

Purpose: To understand the association between anatomical parameters of healthy eyes and optical coherence tomography (OCT) circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurements. Methods: OCT cpRNFL thickness was obtained from 396 healthy eyes in a commercial reference database (RDB). The temporal quadrant (TQ), superior quadrant (SQ), inferior quadrant (IQ), and global (G) cpRNFL thicknesses were analyzed. The commercial OCT devices code these values based on percentiles (red, <1%; yellow, ≥1% and <5%), after taking age and disc area into consideration. Four anatomical parameters were assessed: fovea-to-disc distance, an estimate of axial length, and the locations of the superior and the inferior peaks of the cpRNFL thickness curve. Pearson correlation values were obtained for the parameters and the thickness measures of each of the four cpRNFL regions, and t-tests were performed between the cpRNFL thicknesses coded as abnormal (red or yellow, <5%) versus normal (≥5%). Results: For each of the four anatomical parameters, the correlation with the thickness of one or more of the TQ, SQ, IQ, and G regions exceeded the correlation with age or disc area. All four parameters were significantly (P < 0.001) associated with the abnormal cpRNFL values. The significant parameters were not the same for the different regions; for example, a parameter could be negatively correlated for the TQ but positively correlated with the SQ or IQ. Conclusions: In addition to age and disc area, which are used for inferences in normative databases, four anatomical parameters are associated with cpRNFL thickness. Translational Relevance: Taking these additional anatomical parameters into consideration should aid diagnostic accuracy.

Characteristics of a Large Database of Healthy Eyes From Optometry Practices: Implications for a Real-World Reference Database.

Purpose: To compare an optical coherence tomography (OCT) real-world reference database (RW-RDB) of "healthy" eyes obtained from optometry practices to a commercial reference database (RDB). Methods: OCT scans from 6804 individuals 18 years and older were sampled from a larger database tested at 10 optometry practices involved in refractive and screening services. Employing a reading center method, OCT scans from both eyes of 4932 (4.9K) individuals were judged to be of acceptable quality with an absence of pathology. The 4.9K RW-RDB was compared to a commercial RDB with 398 eyes (398 RDB). Results: The means and distributions of global circumpapillary retinal nerve fiber layer (G-cpRNFL) and global ganglion cell layer (G-GCL) thickness, as well as five key anatomical parameters affecting cpRNFL thickness, were not significantly different for all but one parameter (fovea-to-disc distance) and one thickness metric (G-cpRNFL). In both cases, the difference amounted to less than 1.5%. By design, the number of 4.9K RW-RDB eyes 70 years and older (724, 14.7%) was greater than for the 398 RDB (40, 10.1%). The error bands on the 5% and 1% quantile regression lines (QRLs) were substantially narrower for the 4.9K RW-RDB. Conclusions: The 398 RDB and 4.9K RW-RDB have similar characteristics and appear to come from a similar population. However, the large size of the 4.9K RW-RDB leads to narrower error bands of the QRLs, which has the potential to increase accuracy. Translational Relevance: The larger RW-RDB offers the opportunity to better characterize healthy eyes for clinical diagnosis and clinical trials by furthering our understanding of the patterns of artifacts, exploring covariates, developing separate RW-RDBs, and/or improving AI models.

Understanding Patterns of Preserved Retinal Ganglion Cell Layer in Advanced Glaucoma as Seen With Optical Coherence Tomography.

PRCIS: Using optical coherence tomography (OCT), eyes with advanced glaucoma were found to have a wide range of patterns of damage that were consistent with the natural history of progression based on a model of macular progression. PURPOSE: To understand the patterns of preserved retinal ganglion cells in eyes with advanced glaucoma using OCT and a model of progression of the central macula. METHODS: OCT GCL thickness was measured in 94 eyes with advanced glaucoma, defined as glaucomatous eyes with a 24-2 MD (mean deviation) worse than -12 dB. A commercial report supplied the GCL thickness in 6 sectors of the thick, donut-shaped GCL region around the fovea. For each eye, the 6 sectors were coded as green (within normal limits, WNL), yellow (≤5th, ≥1st percentile), or red (<1st percentile). RESULTS: In all 94 eyes, one or more of the 6 sectors of the donut were abnormal (red or yellow), while all 6 sectors were red in 52 (55%) of the eyes. On the other hand, 33 eyes had one or more sectors WNL (green). While the pattern of donut damage varied widely across these 33 eyes, 61 of the 66 hemiretinas were consistent with a temporal-to-nasal progression of damage within each hemiretina as predicted by our model. CONCLUSIONS: All eyes with advanced glaucoma had damage to the critically important central, donut-shaped GCL region. This region showed a wide range of patterns of damage, but these patterns were consistent with the natural history of progression based on a model of macular progression. These results have implications for the clinical identification of macular progression, as well as for inclusion criteria for clinical trials seeking to preserve central macular function.

Improving glaucoma staging in clinical practice by combining the ICD-10 glaucoma severity classification system and optical coherence tomography.

OBJECTIVE: The International Classification of Disease, 10th revision (ICD-10) codes used for glaucoma severity classification are based on the 24-2 visual-field (VF) test. This study aim was to assess the added value of providing clinicians with optical coherence tomography (OCT) data, in addition to functional data, for glaucoma staging in clinical practice. EXPOSURE: Disease classification was determined for 54 glaucoma eyes, according to the principles of the ICD-10 guidelines. Eyes were independently graded in a masked fashion using the 24-2 VF test and 10-2 VF test, with and without OCT information. The reference standard (RS) for severity was determined using a previously published automated structure-function topographic agreement for glaucomatous damage using all available information. RESULTS: The RS classified eyes as mild, moderate and advanced in 3, 16 and 35 cases, respectively. Individual and combined 24-2 and 10-2 based gradings were significantly different from the RS (all P < 0.005), with Kappa agreements of 0.26, 0.45 and 0.42 respectively (P < 0.001). Classifications using OCT combined with either of the VF were not-significantly different from the RS (P > 0.3) with Kappa agreements of 0.56 and 0.57 respectively (P < 0.001). Combining 24-2 with OCT had less severity overestimations while 10-2 with OCT had fewer underestimations. CONCLUSION: Combining OCT and VF data provides better staging of glaucoma severity than VF data alone. The 24-2 and OCT combination seems most appropriate given the high concordance with the RS and less overestimation of severity. Incorporating structural information into disease stages allows clinicians to set more appropriate severity-based treatment targets for individual patients.

Detecting Established Glaucoma Using OCT Alone: Utilizing an OCT Reading Center in a Real-World Clinical Setting.

Purpose: We evaluated the ability of an optical coherence tomography (OCT)-based reading center for glaucoma (ORG) to detect established glaucoma using OCT alone. Methods: This study included eyes from 70 consecutive patients with established glaucoma (i.e. moderate or severe glaucoma according to the International Classification of Diseases [ICD]-10 guidelines) and 20 consecutive healthy subjects, who had no evidence of glaucomatous optic neuropathy (GON) or visual field (VF) loss in either eye. Using a standardized ORG quality assessment, 33 eyes were excluded due to media opacity (12), poor image quality (13), or epiretinal membrane (8). Of the remaining 147 eyes, 86 had established glaucoma and 36 were from healthy controls (total n = 122). Based on the OCT report alone and applying a previously described evaluation method, the presence of GON in each eye was determined by two masked ORG graders. The main outcome measures were sensitivity and specificity for detection of eyes with established glaucoma. Results: Of the 86 eyes with established glaucoma (average mean deviation [MD] = -10.9 ± 7.7 dB, range = -0.5 to -31.5 dB), only one eye (MD = -0.46) was missed (sensitivity = 98.8%). However, the other eye of this patient was correctly classified as GON. Therefore, at a patient level, sensitivity was 100%. None of the 36 healthy eyes was classified as GON by the ORG (specificity = 100%). Conclusions: An OCT-based reading center is able to identify eyes with established glaucoma using OCT alone with high sensitivity and specificity. Translational Relevance: Our study validates the use of a systematic OCT-based approach for glaucoma detection in a real-world setting.

Evaluation of inner retinal layers in patients with multiple sclerosis or neuromyelitis optica using optical coherence tomography.

PURPOSE: To evaluate the thickness of the inner retinal layers in the macula using frequency-domain optical coherence tomography (fd-OCT) in patients with demyelinating diseases. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 301 eyes of 176 subjects were evaluated. Subjects were divided in 5 different groups: controls, neuromyelitis optica (NMO), longitudinally extensive transverse myelitis (LETM), multiple sclerosis with a history of optic neuritis (MS-ON), and multiple sclerosis without a history of optic neuritis (MS non-ON). METHODS: The individual layers from macular fd-OCT cube scans were segmented with an automated algorithm and then manually hand-corrected. For each scan, we determined the thickness of the retinal nerve fiber layer (RNFL), the combined retinal ganglion cell and inner plexiform layers (RGCL+), and the inner nuclear layer (INL). MAIN OUTCOME MEASURES: Macular RNFL, RGCL+, and INL thickness. RESULTS: The RNFL was significantly thinner than in controls for all patient groups (P ≤ 0.01). Macular RGCL+ thickness was significantly thinner than in controls for the NMO, MS-ON, and MS non-ON groups (P<0.001 for the 3 groups). The INL thickness was significantly thicker than in controls for the patients with NMO (P = 0.003) and LETM (P = 0.006) but not for those with MS-ON or MS non-ON. Although the RNFL and RGCL+ were not significantly different between the NMO and MS-ON groups, the patients with NMO had a significantly thicker INL than the patients with MS-ON (P = 0.02). CONCLUSIONS: Macular RNFL and RGCL+ demonstrate axonal and neural loss in patients with MS, either with or without ON, and in patients with NMO. In addition, the INL thickening occurs in patients with NMO and patients with LETM, and study of this layer may hold promise for differentiating between NMO and MS.

Unilateral retinopathy secondary to occult primary intraocular lymphoma.

PURPOSE: The purpose of the study is to report the clinical case of a 53-year-old woman whose presenting manifestation of primary intraocular lymphoma (PIOL) was unilateral retinal degeneration. METHOD: A case report was created with review of clinical, imaging, electrophysiologic, and pathological investigations. RESULTS: A 53-year-old woman with a distant history of ocular herpes simplex developed progressive central visual loss and intermittent photopsia over 4 years in her right eye. Ophthalmic examination revealed reduced visual acuity OD, central scotoma, and minimal ocular findings. Autofluorescence and infrared imaging revealed mild reflectance changes in the temporal macula, and spectral-domain optical coherence tomography identified mild disruptions of inner segment/outer segment junctions in the subfoveal region of the right eye. A mild window defect was seen on fluorescein angiography. Electrophysiology with multifocal electroretinogram (ERG) revealed evidence of unilateral macular dysfunction. Full-field ERGs revealed progressive global retinal dysfunction over 6 months, with unilateral decreases in amplitude and implicit time shifts, as seen in cases of autoimmune retinopathies. The eye eventually exhibited mild vitreous cellular infiltration on ophthalmoscopic examination, and vitrectomy diagnosed B cell non-Hodgkin's lymphoma. Further evaluation revealed no evidence of central nervous system or systemic disease, consistent with occult PIOL. CONCLUSIONS: This case illustrates an atypical presentation of PIOL characterized by unilateral retinal disease presenting with symptoms and signs of macular dysfunction. Clinical and ERG features evolved into an acute zonal occult outer retinopathy (AZOOR)-like phenotype. PIOL should be considered in atypical cases of AZOOR with vitreal reactions, and some cases of AZOOR may be related to B cell lymphocyte disorders.

Pattern electroretinogram in neuromyelitis optica and multiple sclerosis with or without optic neuritis and its correlation with FD-OCT and perimetry.

PURPOSE: To evaluate the ability of transient pattern electroretinogram (PERG) parameters to differentiate between eyes of patients with neuromyelitis optica (NMO), longitudinally extensive transverse myelitis (LETM), multiple sclerosis with optic neuritis (MS + ON), multiple sclerosis without optic neuritis (MS - ON), and controls, to compare PERG and OCT with regard to discrimination ability, and to assess the correlation between PERG, FD-OCT, and visual field measurements (VFs). METHODS: Visual field measurements and full-field stimulation PERGs based on both 48- and 14-min checks were obtained from patients with MS (n = 28), NMO (n = 20), LETM (n = 18), and controls (n = 26). In addition, FD-OCT peripapillary retinal nerve fiber layer (RNFL) and segmented macular layer measurements were obtained and their correlation coefficients were determined. RESULTS: Compared to controls, PERG amplitude measurements were significantly reduced in eyes with NMO and MS + ON, but not in eyes with LETM and MS - ON. PERG amplitudes were significantly smaller in NMO and MS + ON eyes than in MS - ON eyes. PERG and OCT performance was similar except in NMO eyes where macular thickness parameters were more efficient at detecting abnormalities. A significant correlation was found between N95 amplitude values and OCT-measured macular ganglion cell layer thickness, total retinal thickness, and temporal peripapillary RNFL thickness. PERG amplitude was also significantly associated with VF sensitivity loss. No statistically significant difference was observed with regard to the best-performing parameters of the two methods. CONCLUSIONS: Pattern electroretinogram measurements were able to detect RNFL loss in MS + ON and NMO eyes, with a performance comparable to OCT. PERG amplitude measurements were reasonably well correlated with OCT-measured parameters.

Progression of Early Glaucomatous Damage: Performance of Summary Statistics From Optical Coherence Tomography and Perimetry.

Purpose: Performance comparison of optical coherence tomography (OCT) and visual field (VF) summary metrics for detecting glaucomatous progression. Methods: Thirty healthy control eyes (mean deviation [MD], -1.25 ± 2.03; pattern standard deviation [PSD] , 1.78 ± 0.77) and 91 patient eyes comprised of 54 glaucoma patients and 37 glaucoma suspects (MD, -1.58 ± 1.96; PSD, 2.82 ± 1.92) with a follow-up of at least 1 year formed a group to evaluate progression with event analyses (P-Event). A subset of eyes with an additional criterion of a minimum of four tests was used for trend analyses (P-Trend) (30 healthy controls and 73 patients). For P-Event analysis, test-retest variability thresholds (lower 5th percentile) were estimated with repeat tests within a 4-month period. A P-Event eye was considered a "progressor" if the difference between follow-up and baseline tests exceeded the variability thresholds. For the P-Trend analysis, rates of change were calculated based on least-squares regression. Negative rates with significant (P < 0.05) values were considered progressing. For a reference standard, 17 patient eyes were classified as definitely progressing based on clear evidence of structural and corresponding functional progression. Results: Isolated OCT and VF summary metrics were either inadequately sensitive or not too specific. Combinations of OCT-OCT and OCT-VF metrics markedly improved specificity to nearly 100%. A novel combination of OCT metrics (circumpapillary retinal nerve fiber layer and ganglion cell layer) showed high precision, with 13 of the 15 statistical progressors confirmed as true positives. Conclusions: Although relying solely on metrics is not recommended for clinical purposes, in situations requiring very high specificity and precision, combinations of OCT-OCT metrics can be used. Translational Relevance: All available OCT and VF metrics can miss eyes with progressive glaucomatous damage and/or can falsely identify progression in stable eyes.