Outer retinal abnormalities associated with inner retinal pathology in nonglaucomatous and glaucomatous optic neuropathies.

Inner and outer retinal morphology were quantified in vivo for 6 nonglaucomatous and 10 glaucomatous optic neuropathy patients. Custom, ultrahigh-resolution imaging modalities were used to evaluate segmented retinal layer thickness in 3D volumes (Fourier-domain optical coherence tomography), cone photoreceptor density (adaptive optics fundus camera), and the length of inner and outer segments of cone photoreceptors (adaptive optics-optical coherence tomography). Quantitative comparisons were made with age-matched controls, or by comparing affected and nonaffected retinal areas defined by changes in visual fields. The integrity of outer retinal layers on optical coherence tomography B-scans and density of cone photoreceptors were correlated with visual field sensitivity at corresponding retinal locations following reductions in inner retinal thickness. The photoreceptor outer segments were shorter and exhibited greater variability in retinal areas associated with visual field losses compared with normal or less affected areas of the same patient's visual field. These results demonstrate that nonglaucomatous and glaucomatous optic neuropathies are associated with outer retinal changes following long-term inner retinal pathology.

Visual field defects in acute optic neuritis--distribution of different types of defect pattern, assessed with threshold-related supraliminal perimetry, ensuring high spatial resolution.

PURPOSE: To assess the pattern and the local spatial frequency distribution of visual field defects (VFDs) in eyes with clinically diagnosed optic neuritis (ON) and their currently unaffected fellow eyes, using threshold-related, slightly supraliminal perimetry, ensuring high spatial resolution. METHODS: Records obtained with the Tübingen Automatic perimeter (TAP, Oculus Inc., Dudenhofen, Germany) and the Octopus 101 perimeter (Haag-Streit Inc, Koeniz, Switzerland), using a standardized grid of 191 static targets within the central 30 degrees visual field, were analysed retrospectively. VFDs were assigned to 15 classes. RESULTS: Visual fields (VF) from 99 patients (26 male and 73 female subjects, aged from 18 to 51 years) with clinically diagnosed, acute ON (52 right eyes, 48 left eyes affected, one bilateral involvement) were evaluated. Central scotomas were the most common finding in associated eyes, covering 41% of all VFDs in affected eyes. Nerve fibre bundle defects were found in 29% and paracentral scotomas in 14% of all VFDs. Fellow eyes were perimetrically normal in 65% of the clinically monocular ONs. Nerve fibre bundle defects were found in 21% and diffuse scotomas in 9% of the fellow eyes. CONCLUSIONS: Central scotomas and retinal nerve fibre bundle defects are the most common VFDs in acute ON. Small central and paracentral scotomas that most probably would have been missed by automated thresholding perimetry with its relatively coarse grid could be detected by threshold-related, slightly supraliminal strategy. Of the fellow eyes in clinically apparent monocular optic neuritis, 35% present with visual field defects.

Clinical and immunologic characteristics of melanoma-associated retinopathy syndrome: eleven new cases and a review of 51 previously published cases.

OBJECTIVE: To evaluate the signs, symptoms, and immune responses of patients with melanoma-associated retinopathy (MAR) syndrome. MATERIALS AND METHODS: We reviewed the clinical and immunologic findings of 62 MAR syndrome patients. They include 25 patients from our institution (11 not previously reported) and 37 patients reported from other institutions. RESULTS: There were 33 men and seven women (no gender information is available for the remaining 22 cases). Age at onset of the visual disturbance averaged 57.5 years (range, 30-78). Visual acuity of 20/60 or better was initially present in 82%. Fundus examination was normal in 44%, optic disc pallor was present in 23%, and retinal vessel attenuation was present in 30%. Vitreous cells were present in 30%. The latency from melanoma diagnosis to recognition of MAR syndrome averaged 3.6 years (range, 2 months to 19 years). Seven patients sustained visual improvement with various treatment regimens, especially with intravenous immunoglobulin and cytoreductive surgery (metastasectomy). Indirect immunohistochemical staining of the bipolar layer was typical, but several other retinal elements were also reactive. Tissue from a metastatic melanoma excised from one of the patients expressed antigens that reacted with antiretinal antibodies. CONCLUSION: MAR syndrome demonstrates diverse clinical and immunologic features. Treatment, especially intravenous immunoglobulin and cytoreductive surgery (metastasectomy), improves vision in some cases.

Confirmation of visual field abnormalities in the Ocular Hypertension Treatment Study. Ocular Hypertension Treatment Study Group.

OBJECTIVE: To determine the frequency with which visual field abnormalities observed on follow-up visual fields for patients in the Ocular Hypertension Treatment Study were confirmed on retest. METHODS: Between April 1, 1994, and March 1, 1999, 21,603 visual fields were obtained from 1637 patients in the Ocular Hypertension Treatment Study. When follow-up visual fields are outside the normal limits on the Glaucoma Hemifield Test, the Corrected Pattern Standard Deviation (P<.05), or both, subsequent follow-up visual fields are monitored to confirm the abnormality. Abnormalities are confirmed if they are again abnormal on the Glaucoma Hemifield Test, the Corrected Pattern Standard Deviation, or both; if the defect is not artifactual; and if the same index and location are involved. Reliability criteria used by the study consisted of a limit of 33% for false positives, false negatives, and fixation losses. RESULTS: Of the 21,603 regular follow-up visual fields, 1006 were follow-up retests performed because of an abnormality (n = 748) or unreliability (n = 258). We found that 703 (94%) of the 748 visual fields were abnormal and reliable, and 45 (6%) were abnormal and unreliable. On retesting, abnormalities were not confirmed for 604 (85.9%) of the 703 originally abnormal and reliable visual fields. CONCLUSIONS: Most visual field abnormalities in patients in the Ocular Hypertension Treatment Study were not verified on retest. Confirmation of visual field abnormalities is essential for distinguishing reproducible visual field loss from long-term variability. Arch Ophthalmol. 2000;118:1187-1194

Comparison of central and peripheral visual field properties in the optic neuritis treatment trial.

PURPOSE: To compare the results of peripheral kinetic visual field testing and central static perimetry for patients enrolled in the Optic Neuritis Treatment Trial to determine (1) whether loss and recovery of visual field sensitivity in the far periphery was different from that observed in the central visual field and (2) whether the far peripheral visual field provided additional useful information that was not available in the central visual field results. METHODS: Both affected and fellow eyes of 448 patients with optic neuritis in the Optic Neuritis Treatment Trial were evaluated according to the trial protocol during the patients' first 3 years in the study. Central static visual field tests were performed with program 30-2 on the Humphrey Field Analyzer, and peripheral kinetic testing consisted of plotting the I3e and II4e isopters on the Goldmann perimeter. Both test procedures were conducted according to the trial protocols, and quality control assessments and clinical evaluations were performed on all the visual fields. RESULTS: For both affected and fellow eyes at all 11 visits, there was a greater number of abnormal visual fields in the central static perimetry results than in the peripheral kinetic data. Only 2.9% of affected eyes had an abnormal peripheral visual field with a normal Humphrey mean deviation during year 1. At baseline, 97.1% of affected eyes had an abnormal Humphrey mean deviation on central static testing, whereas only 69.9% had abnormal peripheral kinetic visual fields. Approximately 80% of the I3e and II4e isopters for affected eyes that were abnormal at baseline were within normal limits at 30 days, but it took until week 19 for even 70% of the Humphrey mean deviations to return to normal. In addition, the II4e isopters (more peripheral than the I3e isopters) that were abnormal at baseline showed a somewhat greater percentage of improvement from baseline through day 30 than the abnormal I3e isopters. Although this difference is statistically significant, it is probably not clinically significant. For visits after week 19, approximately 25% to 30% of affected eyes had an abnormal Humphrey mean deviation, whereas only 10% to 15% of peripheral kinetic fields were abnormal. CONCLUSIONS: For the affected eye in optic neuritis, the central visual field shows greater abnormalities than the far peripheral visual field. When the results obtained through Humphrey automated central static visual fields and Goldmann peripheral kinetic isopters are compared, the far periphery appears to recover more rapidly and more completely than the central field, at least in more severe cases of optic neuritis. In most cases, recovery in optic neuritis can probably be monitored effectively with automated perimetry of the central visual field alone. However, in cases of severe loss of the central visual field, a peripheral kinetic visual field obtained with a Goldmann perimeter may provide additional information about the patient's vision in the far periphery.

The 22-kDa antigen in optic nerve and retinal diseases.

OBJECTIVE: Patients with unexplained visual loss were evaluated for the possibility of immunologic involvement. Antibody reactions were sought that might identify a common indication of retinal hypersensitivity. METHODS: The enzyme-linked immunosorbent assay (ELISA) and Western blot analysis were used to identify autoantibody reactions with retina and optic nerve components. Comparisons were made with the autoantibody reaction of normal subjects and patients with recognized forms of retinal decay: macular degeneration, retinitis pigmentosa, diabetic retinopathy, and paraneoplastic retinopathy. RESULTS: Eight patients, one man and seven women, were found to produce an autoantibody reaction with retina and optic nerve, including a novel 22-kDa neuronal antigen present within the retina and optic nerve. One of the eight had retinopathy associated with melanoma (MAR Syndrome). Seven of the eight patients had electroretinogram abnormalities, varying from mild to severe. Six displayed features of optic atrophy. One patient with progressive visual loss had visual function stabilized after immunosuppressive therapy. CONCLUSIONS: In the eight cases described, unexplained visual loss was associated with autoantibody reactions with retina and optic nerve, including a common antibody reaction with a 22-kDa neuronal antigen found in the retina and optic nerve. All the patients had either an abnormal electroretinogram or optic atrophy. Six patients had both. The 22-kDa immunologic marker may not be directly involved in the patient's vision loss, but rather may be related to a nonspecific destruction of retina and optic nerve. However, the marker may be useful in identifying a specific subgroup of patients for further analysis.

Paraneoplastic optic neuropathy and autoantibody production in small-cell carcinoma of the lung.

A 59-year-old woman presented with acute-onset, bilateral, painless loss of vision, dysarthria, and ataxia. Ophthalmoscopy showed bilateral optic disc edema. A magnetic resonance scan of the head was normal. Chest radiography showed mediastinal adenopathy. Mediastinoscopy and biopsy identified small-cell carcinoma of the lung. An autoantibody to optic nerve and retina was demonstrated in the patient's serum. An electroretinogram was normal. The patient was diagnosed with a paraneoplastic optic neuropathy and paraneoplastic cerebellar syndrome. After treatment for her lung cancer, the patient remains stable from a visual and neurologic standpoint.

Long- and short-term variability of automated perimetry results in patients with optic neuritis and healthy subjects.

OBJECTIVE: To measure the short- and long-term variability of automated perimetry in patients with optic neuritis and normal subjects. DESIGN: Prospective case-control design of patients with recovered optic neuritis with intraday and interday repetitions to obtain robust variability measurements. Entry criteria included a corrected pattern SD that was worse than the normal 5% probability level and a mean deviation worse than -3 dB but better than -20 dB. Five Humphrey 30-2 full threshold tests were administered during a 7-hour period (1 test every 2 hours) on the same day and at the same periods on 5 separate days. SUBJECTS: Seventeen patients with recovered optic neuritis and 10 healthy subjects of similar age. MAIN OUTCOME MEASURES: Short-term variability and long-term variability for global visual field data. RESULTS: Patients with optic neuritis demonstrated variations in visual field sensitivity that were outside the entire range of variability for normal controls. These variations occurred for multiple tests performed on the same day at specific times and for tests performed at specific times on different days. There were no consistent patterns of sensitivity changes that could be attributed to time of day. The most dramatic fluctuations occurred in a patient whose visual fields varied from normal to a hemianopic defect from one week to another and from a partial quadrant loss to a hemianopic defect at different times on the same day. Seven of the patients with optic neuritis also demonstrated intermittent vertical step defects. CONCLUSIONS: Patients with resolved optic neuritis can have large variations in visual field results on different days and at different times on the same day. The variations affect both the severity and the pattern of visual field loss and do not appear to be consistent across patients. These data indicate that care must be taken when automated visual field results in patients with optic neuritis are interpreted. Distinguishing systematic changes in sensitivity from variability requires more than a comparison of the current visual field with the most recent previous visual field.

The variable expressivity of a family with central areolar pigment epithelial dystrophy.

PURPOSE: To clarify the nosology of autosomal dominant central areolar pigment epithelial dystrophy (CAPED) as previously described. METHODS: The authors studied a family of 69 members spanning six generations with a macular dystrophy. Thirty-four patients were examined, and those found to be affected underwent further testing, including visual fields, electrophysiologic studies, and fluorescein angiography. Family history and medical records were used in three additional deceased patients. RESULTS: Eleven patients were identified as having CAPED. The phenotype was inherited in an autosomal dominant fashion. Six of these patients were examined by us and had mid-life onset (at 32-53 years) of progressive visual loss (20/50--counting fingers), occurring over a 3- to 10-year period. These subjects had circumscribed hypopigmented maculae, retinal pigment epithelial window defects on fluorescein angiography, central scotomas, and electrophysiologic studies, ranging from normal to severely abnormal. Three deceased patients were presumed to have CAPED by review of records or family history. Two additional patients examined had mild macular changes but good visual acuity and no significant abnormalities on electrophysiologic studies. The latter two patients are presumed to have had early manifestations of CAPED. CONCLUSION: This family demonstrates that CAPED is an autosomal-dominant hereditary macular dystrophy which has late-onset and variable expressivity.

Short-wavelength automated perimetry in neuro-ophthalmologic disorders.

OBJECTIVE: To evaluate the efficacy of short-wavelength automated perimetry (SWAP) in the assessment of patients with neuro-ophthalmologic disorders, especially optic neuropathies. METHODS: A modified Humphrey field analyzer was used to perform standard automated perimetry and SWAP, a technique that isolates the activity of short-wavelength-sensitive ("blue") mechanisms. Forty patients (80 eyes) were evaluated by SWAP and standard automated perimetry. Thirteen patients (26 eyes) had recovered from optic neuritis and/or multiple sclerosis, 15 (30 eyes) were in various stages of treatment for pseudotumor cerebri, and 12 (24 eyes) had other miscellaneous neuro-ophthalmologic conditions. Six additional patients (12 eyes) with neuro-ophthalmologic conditions were tested twice on different days during a 2-week period, with the order of SWAP and standard perimetric testing being reversed on the second day. RESULTS: Of the 80 eyes tested, 38 (48%) had SWAP visual fields that were worse than standard automated perimetry results; 29 (36%) showed no difference between standard and SWAP visual fields; and 13 (16%) had standard automated perimetry results that were worse than SWAP visual fields. Of the 26 eyes in patients with optic neuritis and/or multiple sclerosis, 15 (58%) had SWAP results that were worse than standard visual fields. Ten (33%) of the 30 eyes with pseudotumor cerebri had SWAP results worse than standard automated perimetry results, and 13 (54%) of 24 eyes with miscellaneous neuro-ophthalmologic conditions had SWAP results worse than standard automated perimetry results. For the 12 eyes undergoing repeated testing, SWAP visual fields were worse when they were performed last, perhaps indicating that some fatigue effect was present. This was observed for standard visual fields as well, but to a smaller extent. CONCLUSIONS: Preliminary findings suggest that SWAP may be useful in detecting certain neuro-ophthalmologic deficits more readily than standard automated visual field testing, especially for optic neuritis and multiple sclerosis. Further evaluations will be necessary to define the effects of fatigue for SWAP visual fields in neuro-ophthalmologic disorders.

Visual field profile of optic neuritis. One-year follow-up in the Optic Neuritis Treatment Trial.

PURPOSE: The purpose of this present study was to evaluate longitudinal visual field information for 448 patients over their first year of follow-up in the Optic Neuritis Treatment Trial. METHODS: We reviewed 6536 automated static visual fields performed on a visual field analyzer (Humphrey Visual Field Analyzer) at nine visits within the 1-year period for each of the patients. RESULTS: The median values of the mean deviations for affected eyes were as follows: -22.88 dB at baseline, -1.94 dB at 6 months, and -1.62 dB at 1 year. At 6 months, 51% of affected eye visual fields were normal, and at 1 year 55.9% were normal. Approximately two thirds (68.8%) of the fellow eyes were classified as abnormal at baseline, although the defects were generally slight. One third (33.2%) were abnormal at 6 months, and approximately one third were still abnormal at 1 year. More than 87% of those abnormal at 6 months and at 1 year had been abnormal at baseline. Binocular analysis revealed that 13.2% of patients showed a chiasmal or retrochiasmal type of field defect at least once during the year (5.1% bitemporal; 8.9% homonymous). Of the patients who showed a retrochiasmal visual field defect, 75.7% had an abnormal magnetic resonance imaging scan at baseline compared with 46% of the rest of the patients in the Optic Neuritis Treatment Trial (chi 2 = 10.73, df = 1, P < .002). CONCLUSION: Over the first year of follow-up, the majority of patients with visual field defects from acute optic neuritis returned to normal, as measured by automated static perimetry. Many fields showed variation in the pattern and location of the sensitivity loss. Chiasmal and retrochiasmal defects occurred more commonly than previously reported.

Psychosocial aspects of strabismus study.

OBJECTIVE: To assess the psychosocial implications of growing up with and living with socially noticeable strabismus. DESIGN: Self-report mailed questionnaire and the Hopkins Symptom Checklist. SETTING: Patients with strabismus who were seen at the University of California, Davis, Medical Center, Department of Ophthalmology, from 1976 to 1989. PARTICIPANTS: Forty-three female and male subjects aged 15 years or older who had a history of childhood strabismus that was uncorrected or incompletely corrected past the age of 13 years. INTERVENTION: None. MAIN OUTCOME MEASURES: Participants' responses to our survey and to the Hopkins Symptom Checklist. RESULTS: Strabismus had a negative impact on many aspects of our subjects' lives. They report difficulty with self-image, securing employment, interpersonal relationships, school, work, and sports. Furthermore, difficulties encountered did not go away after childhood, rather, the problems encountered by our subjects intensified in the teenage and adult years. Subjects demonstrated generalized higher levels of distress on the Hopkins Symptom Checklist than age- and sex-matched controls (P < .01). CONCLUSIONS: Psychosocial difficulties relating to socially noticeable strabismus are not just a problem for school-children but also for teenagers and adults. Correction of strabismus in the older teenager or adult may offer them improvement in psychosocial functioning, a benefit not previously reported in the literature.

Antibody reactions with retina and cancer-associated antigens in 10 patients with cancer-associated retinopathy.

OBJECTIVE: Our objectives were to determine what clinical characteristics are common to the form of cancer-associated retinopathy (CAR) encountered in patients with small-cell carcinoma of the lung (SCCL). Is the 23-kd retinal CAR antigen/antibody reaction present in other forms of retinopathy? Can an antigen identical or similar to the 23-kd retinal CAR antigen be identified in an established culture of SCCL? METHODS: Ten patients with CAR who had SCCL were identified by their antibody reactivity with the 23-kd retinal CAR antigen. We inquired into common clinical characteristics by means of questionnaires to the referring physicians. We looked for antigen/antibody reactions with the 23-kd retinal CAR antigen in patients with diabetic and age-related macular degenerations and in a continuous, in vitro propagated culture of SCCL (HTB 119) obtained from the American Type Culture Collection. RESULTS: We encountered many similar signs and symptoms in our patient population. These included rapid vision loss, night blindness, color loss, vitreous cells, and either flat or greatly reduced electroretinograms. No corollary to the 23-kd CAR antigen/antibody could be identified in unrelated retinopathies or cultured SCCL. CONCLUSIONS: We conclude that patients with SCCL-related CAR consistently produce antibodies against the 23-kd retinal CAR antigen. This immunologic reaction was not found in patients with unrelated retinopathies and may possibly represent a cancer marker for SCCL.

Intraperitoneal cultivation of small-cell carcinoma induces expression of the retinal cancer-associated retinopathy antigen.

OBJECTIVE: We have inquired into the reason why patients with cancer-associated retinopathy (CAR) produce antibody reactions with the 23-kd retinal CAR antigen. Possible reasons include the expression of this antigen in the related carcinoma. Previous studies have failed to identify any antigenic counterpart expressed by in vitro cultivated small-cell carcinoma of the lung. We, therefore, inquired into the effects of in vivo cultivation of the cancer cells and its influence on protein expression, with specific reference to the appearance of the 23-kd retinal CAR antigen. DESIGN: A complementary DNA library was prepared from small-cell carcinoma of the lung cells propagated intraperitoneally in Lewis rats and probed with antibodies reactive with the 23-kd retinal CAR antigen. RESULTS: We found evidence of the expression of a cancer-associated gene in ascites-propagated small-cell carcinoma of the lung that encodes for a protein antigenically similar to the 23-kd retinal CAR antigen. A complementary DNA encoding this protein revealed complete DNA sequence homology with the retinal CAR antigen showing the cancer cells are expressing this photoreceptor protein. CONCLUSIONS: We hypothesize that the carcinoma-retina immunologic cross-reaction is responsible for the induction of the unique antibody response encountered in patients with CAR with vision loss developing as a cancer-evoked autoimmune retinopathy.

Quality control functions of the Visual Field Reading Center (VFRC) for the Optic Neuritis Treatment Trial (ONTT).

The Visual Field Reading Center (VFRC) was established to assess visual field testing in the Optic Neuritis Treatment Trial (ONTT), to train and certify ONTT technicians, and to monitor the quality of the visual fields through evaluation of the technical aspects of the visual field testing. We describe the functions of the VFRC personnel and the standardized test protocols developed by the VFRC for Humphrey and Goldmann perimetry. We also describe the VFRC procedures for training and certifying visual field technicians, double-checking the eligibility of ONTT patients, assessing the quality of the visual field data, and processing visual field data. In addition, we describe the principles applied by the director and associate director of the VFRC in their clinical classification of the various localized and diffuse visual field defects observed in the Humphrey and Goldmann visual fields. The VFRC has processed more than 14,000 Humphrey and Goldmann visual field tests. The visual field quality control procedures and visual field defect classification process have been shown to be quite reproducible. Through quality control assessment procedures, we have been able to pinpoint a variety of problems at an early stage and promptly implement corrective measures. The standardized test protocols, technician training and certification procedures, and quality control assessment techniques used by the VFRC for the ONTT may serve as a model for future clinical trials employing visual field data as an outcome measure. These procedures can also be used to enhance visual field reliability in ophthalmological practices.

Linear nevus sebaceous syndrome.

The pathologic terms hamartoma, choristoma, nevus, and phakoma often are confused. We discuss them in relation to a patient with the linear nevus sebaceous syndrome who had a large limbal mass that grew unusually rapidly and was excised. Histopathologic examination showed that it was a complex choristoma composed of lacrimal gland, adipose tissue, and myxomatous tissue. The latter has not been described previously in this disorder. This neuro-oculocutaneous syndrome has been considered one of the phakomatoses.