Distant cancer effects on standardised testing of peripheral vision.

BACKGROUND: Profound central-retinal visual losses have been a major presenting factor reported in cancer and melanoma associated retinopathies (CAR, MAR). However, it is well established that standardised tests of peripheral retinal function are often the most sensitive detectors of early eye disease. This is a preliminary investigation of the responsiveness of the peripheral retina to "distant" (non-eye or CNS) cancers using easily obtained standardised tests. METHODS: The design is a single blind study where test results are compared with published norms and a small age matched control group. Of 120 ambulatory cancer outpatients who were interviewed at routine follow up examinations, 111 volunteered and admitted a range of mild visual changes. 25 cancer patients completed all tests of peripheral vision function and a clinical screening. There were seven control subjects of the same age range. RESULTS: 98% (49 of 50) of eyes from the patient cohort were judged clinically normal following examinations which emphasised the central retina, fundus appearance, and static fields. On testing which emphasised the visual periphery, 46 (92%) eyes showed one or more quantitative abnormalities >2 SD from the age adjusted norm means. These abnormalities clustered mainly about dark adaptation (rod cell) sensitivity (31, 62% of measured sites), the blue sensitive retinal cells (17, 34% of measured eyes), and the oscillatory component (OP) of the electroretinogram (23, 46% of measured eyes). One control eye (7%) showed a significant dark adaptation abnormality and ERG reduction. There was no identifiable interaction between chemotherapy mode and the cancer associated retinal deficits (CARD). Antiretinal antibodies were found in sera from most patients and controls. CONCLUSION: CARD is common in the retinal periphery of many cancer patients, and is distinct from rare CAR, MAR central-retinal responses. CARD has numerous potential clinical uses which justify expanded research with more defined large samples.

Autoimmune retinopathy: patients with antirecoverin immunoreactivity and panretinal degeneration.

PURPOSE: To investigate whether antirecoverin antibodies are present in patients with retinitis pigmentosa (RP). Recoverin, a retinal protein, has been implicated as a cause of cancer-associated retinopathy (CAR), which manifests as an RP-like retinal degeneration. The rationale is that the ocular findings in CAR syndrome are similar to those found in many forms of RP, and since 40% of patients with RP have no family history, some patients may have an underlying autoimmune process causing or contributing to their retinopathy. METHODS: Serum samples from 521 patients diagnosed with RP were screened for antiretinal proteins activity by Western blot analysis. Fifty-one patients had antibody reactivity against retinal proteins in the range of 23 to 26 kd and underwent dot-blot analysis for antirecoverin antibody, checking IgG and IgM antibodies. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate the titer of antirecoverin antibodies in patients with positive results on dot-blot analysis. Lymphocyte proliferation assays using recoverin were performed on 26 samples. RESULTS: Ten patients were found to have antirecoverin antibody and/or cellular immunoreactivity. Eight patients had positive dot-blot testing: 6 patients had both IgG and IgM antirecoverin activity, and 1 patient each had IgG or IgM activity. In these 8 patients, numerous other antiretinal protein antibodies were present. Three patients had positive recoverin-mediated lymphocyte proliferation, and all patients were positive for antirecoverin antibodies on ELISA testing. CONCLUSIONS: Antirecoverin immunoreactivity was found in 10 patients without systemic malignancy but with clinical findings consistent with RP. These results suggest that there are other immunogenic mechanisms occurring in the formation of antirecoverin antibodies in addition to the putative tumor-mediated mechanisms. This survey suggests that there may be rare cases of CAR-like syndrome in the category of simplex RP, or that some patients with RP also have antirecoverin antibodies that may be exacerbating their underlying disease. Arch Ophthalmol. 2000;118:1525-1533

Association of antiretinal antibodies and cystoid macular edema in patients with retinitis pigmentosa.

PURPOSE: To report the association of antiretinal antibodies in patients with bilateral cystoid macular edema and retinitis pigmentosa. METHODS: In a prospective study, 30 consecutive patients with bilateral cystoid macular edema and retinitis pigmentosa were tested for antiretinal antibodies. As control subjects, 30 consecutive patients with retinitis pigmentosa who did not have cystoid macular edema and 50 normal subjects without retinitis pigmentosa or cystoid macular edema were tested for antiretinal antibodies. Laboratory personnel performing the antiretinal antibody testing were masked regarding the diagnosis of each patient. RESULTS: Twenty-seven (90%) of 30 patients with retinitis pigmentosa with cystoid macular edema had antiretinal protein antibody activity, compared with three (6%) of 50 normal controls (P < .001) and only four (13%) of 30 control patients with retinitis pigmentosa (P < .001). CONCLUSIONS: We found a significant association between cystoid macular edema and the presence of circulating antiretinal antibodies in patients who presented with retinitis pigmentosa and cystoid macular edema. This study suggests that patients with retinitis pigmentosa with cystoid macular edema may have an autoimmune process that is contributing to the formation of cystoid macular edema in retinitis pigmentosa, but to date, there is no direct evidence that the cystoid macular edema is caused by the antiretinal antibodies.

Voltage- and GABA-evoked currents from Müller glial cells of the baboon retina.

The electrophysiological features of isolated baboon Müller cells was investigated using the whole-cell voltage-clamp technique. Application of depolarizing voltage steps evoked transient inward and delayed outward currents. The transient currents disappeared when extracellular Na+ was replaced by choline+ and were substantially decreased by application of tetrodotoxin (1 microM). The outward currents were strongly diminished by extracellular Ba2+ (1 mM), and the hyperpolarization-generated inward currents disappeared following application of Ba2+. The recently described gamma-aminobutyric acid A (GABAA) receptor currents were increased by flunitrazepam, nordiazepam, pentobarbital and Zn2+, as well as by the inverse agonist DMCM. These results suggest that the baboon Müller cells possess the same voltage-dependent current pattern as those from other species, e.g. humans, whereas their GABAA receptors react in an uncharacteristic manner to DMCM and Zn2+, when compared with neuronal GABAA receptors.

GABAA receptor currents recorded from Müeller glial cells of the baboon (Papio cynocephalus) retina.

The effect of gamma-aminobutyric acid (GABA) application on acutely isolated, non-cultivated Muller glial cells from the baboon retina was studied using the whole-cell voltage-clamp technique. Application of GABA (0.1 mM) generated inward currents at a holding potential of -80 mV as well as an increase in current noise. The GABA-activated current had a reversal potential of 18.6 mV and was therefore supposed to be a Cl- current (ECl = 5 mV). The GABAA receptor agonist muscimol (0.1 mM) elicited an inward current and bicucullin (0.5 mM), a blocker of the GABAA receptor, diminished the GABA responses in our experiments completely. Baclofen (0.1 mM), a GABAB agonist, neither had an effect when applied under conditions where the dominant Muller cell K+ currents were unblocked, nor when the K+ currents were blocked by application of Ba2+ (1 mM). Glycine (0.1 mM) was ineffective as well. From these results we conclude that the baboon retinal Muller cells possess GABAA receptors. However, these have recently been discovered on skate Muller cells whereas GABAA receptors could not be found on Muller cells of guinea pig, pig, mouse, rat and rabbit.