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PURPOSE: To investigate peripapillary atrophy and macular chorioretinal scars in eyes affected by multifocal choroiditis and panuveitis (MCP). METHODS: This retrospective cohort study reviewed the medical records, fundus photographs, and SD-OCT scans of 31 eyes from 19 patients. RESULTS: Patients had a mean age of 45 years (range 24-69 years). The average follow-up duration was 7 years (range 2.5-14.5 years), with 14 patients undergoing immunosuppressive treatment. In the group of 31 eyes, 20 showed peripapillary plumes of ill-defined hyperreflectivity at the termination border of the retinal pigment epithelium (RPE). These plumes, extending from bare Bruch's membrane to the outer nuclear layer, sometimes undermined the adjacent RPE. They responded to corticosteroid treatment and resembled the material under the RPE in acute lesions. Among 20 eyes with these peripapillary inflammatory lesions, 16 (80%) experienced increased atrophy, in contrast to none in the eyes without these lesions (P<0.001). Similar patterns were observed at the edges of macular chorioretinal atrophy. This observation occurred in patients using immunosuppressive medication who were otherwise thought to be under adequate control. CONCLUSION: In MCP patients, previously unrecognized plumes of smoldering inflammatory activity at the borders of chorioretinal atrophy appears to be linked to atrophy expansion. The recognition of this phenomenon may require a reappraisal of treatment of multifocal choroidopathies to help mitigate expansion of atrophy in these eyes.
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PURPOSE: To describe a severe recurrence of intraocular inflammation following the cessation of immunosuppression, previously administered for multifocal choroiditis and panuveitis (MCP). METHODS: Retrospective chart review. RESULTS: A 27-year-old woman with MCP initially was treated with intravenous and oral corticosteroids and photodynamic therapy because of an active macular neovascularization in both eyes. Mycophenolate was soon started and the recurrences during tapering of the oral corticosteroids in the first months were treated with periocular corticosteroids and anti-vascular endothelial growth factor injections as they became available. After a decade of immunosuppression without recurrences, the patient, having relocated, discontinued mycophenolate upon the advice of a new ophthalmologist who diagnosed her with punctate inner choroidopathy. This led to a severe recurrence in both eyes, characterized by new inflammatory lesions, ellipsoid zone loss, and widespread inflammatory cell infiltration into the outer retina. Intravitreal triamcinolone injections resulted in the resolution of sub- and intraretinal inflammatory lesions and ellipsoid zone defects. CONCLUSION: The abrupt discontinuation of immunosuppression in a patient with MCP was associated with a rebound phenomenon, characterized by multi-level inflammatory activity in the posterior pole. This rebound phenomenon may offer clues as to the inflammatory targets in MCP.
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BACKGROUND: Pseudoxanthoma elasticum (PXE), a monogenic disorder resulting in calcification affecting the skin, eyes and peripheral arteries, is caused by mutations in the ABCC6 gene, and is associated with low plasma inorganic pyrophosphate (PPi). It is unknown how ABCC6 genotype affects plasma PPi. METHODS: We studied the association of ABCC6 genotype (192 patients with biallelic pathogenic ABCC6 mutations) and PPi levels, and its association with the severity of arterial and ophthalmological phenotypes. ABCC6 variants were classified as truncating or non-truncating, and three groups of the 192 patients were formed: those with truncating mutations on both chromosomes (n = 121), those with two non-truncating mutations (n = 10), and a group who had one truncating and one non-truncating ABCC6 mutation (n = 61). The hypothesis formulated before this study was that there was a negative association between PPi level and disease severity. RESULTS: Our findings confirm low PPi in PXE compared with healthy controls (0.53 ± 0.15 vs. 1.13 ± 0.29 µM, p < 0.01). The PPi of patients correlated with increasing age (ß: 0.05 µM, 95% CI: 0.03-0.06 per 10 years) and was higher in females (0.55 ± 0.17 vs. 0.51 ± 0.13 µM in males, p = 0.03). However, no association between PPi and PXE phenotypes was found. When adjusted for age and sex, no association between PPi and ABCC6 genotype was found. CONCLUSIONS: Our data suggest that the relationship between ABCC6 mutations and reduced plasma PPi may not be as direct as previously thought. PPi levels varied widely, even in patients with the same ABCC6 mutations, further suggesting a lack of direct correlation between them, even though the ABCC6 protein-mediated pathway is responsible for ~60% of this metabolite in the circulation. We discuss potential factors that may perturb the expected associations between ABCC6 genotype and PPi and between PPi and disease severity. Our findings support the argument that predictions of pathogenicity made on the basis of mutations (or on the structure of the mutated protein) could be misleading.
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Purpose: To describe the natural history of Bruch's membrane (BM) calcification in patients with pseudoxanthoma elasticum (PXE). Design: Retrospective cohort study. Participants: Both eyes of 120 PXE patients younger than 50 years, 78 of whom had follow-up imaging after more than 1 year. Methods: All patients underwent multimodal imaging, including color fundus photography, near-infrared reflectance (NIR) imaging, and late phase indocyanine green angiography (ICGA). We determined the distance from the optic disc to the central and temporal border of peau d'orange on NIR, expressed in horizontal optic disc diameter (ODD). The length of the longest angioid streak was classified into 5 zones. Main Outcome Measures: Age-specific changes of peau d'orange, angioid streaks, and ICGA hypofluorescence as surrogate markers for the extent of BM calcification. Results: In cross-sectional analysis, longer angioid streaks were associated with increasing age (P < 0.001 for trend). The temporal border of peau d'orange showed a weak association with increasing age (ß = 0.02; 95% confidence interval [CI], 0.00-0.04), whereas the central border showed a strong association (ß = 0.12; 95% CI, 0.09-0.15). Longitudinal analysis revealed a median shift of the central border to the periphery of 0.08 ODD per year (interquartile range [IQR], 0.00-0.17; P < 0.001). This shift was more pronounced in patients younger than 20 years (0.12 ODD per year [IQR, 0.08-0.28]) than in patients older than 40 years (0.07 ODD per year [IQR, -0.05 to 0.15]). The temporal border did not shift during follow-up (P = 0.69). New or growing angioid streaks were detected in 39 of 156 eyes (25%). The hypofluorescent area on ICGA was visible only in the fourth or fifth decade and correlated with longer angioid streaks. Conclusions: In PXE patients, the speckled BM calcification slowly confluences during life. The location of the temporal border of peau d'orange remains rather constant, whereas the central border shifts to the periphery. This suggests the presence of a predetermined area for BM calcification. A larger ICGA hypofluorescent area correlates with older age and longer angioid streaks, which implies that it depends on the degree of BM calcification.