Reversal of threatening blindness after initiation of eculizumab in Purtscher-like retinopathy secondary to atypical hemolytic uremic syndrome.

Purtscher-like retinopathy, a rare manifestation of systemic thrombotic microangiopathy, is a potentially visually debilitating condition with no effective proven treatment. Distinct pathogenic pathways have been proposed as etiological factors. We revisit the etiology of Purtscher-like retinopathy based on the rapid response and profound visual improvement after initiation of systemic intravenous eculizumab, an inhibitor of the complement cascade, in a patient with Purtscher-like retinopathy secondary to familial atypical hemolytic uremic syndrome (aHUS) due to a mutation in complement factor H. We hypothesize that the efficacy of eculizumab in this patient provides evidence for pathogenic events in the retina similar to those encountered in the renal microvasculature of aHUS patients, namely complement-mediated thromboembolization as a result of activation of the complement cascade in endothelial cells with release of tissue factor and development and amplification of a procoagulant state. To the best of our knowledge, this is the first report in the literature of eculizumab as an effective therapeutic strategy in Purtscher-like retinopathy.

Identification of mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa.

OBJECTIVE: To identify mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa. METHODS: Mutation analysis was carried out in a group of 35 unrelated patients with juvenile autosomal recessive retinitis pigmentosa (ARRP), Leber's congenital amaurosis (LCA), or juvenile isolated retinitis pigmentosa (IRP), by denaturing high performance liquid chromatography followed by direct sequencing. RESULTS: All three groups of patients showed typical combinations of eye signs associated with retinitis pigmentosa: pale optic discs, narrow arterioles, pigmentary changes, and nystagmus. Mutations were found in 34% of PATIENTS: in CRB1 (11%), GUCY2D (11%), RPE65 (6%), and RPGRIP1 (6%). Nine mutations are reported, including a new combination of two mutations in CRB1, and new mutations in GUCY2D and RPGRIP1. The new GUCY2D mutation (c.3283delC, p.Pro1069ArgfsX37) is the first pathological sequence change reported in the intracellular C-terminal domain of GUCY2D, and did not lead to the commonly associated LCA, but to a juvenile retinitis pigmentosa phenotype. The polymorphic nature of three previously described (pathological) sequence changes in AIPL1, CRB1, and RPGRIP1 was established. Seven new polymorphic changes, useful for further association studies, were found. CONCLUSIONS: New and previously described sequence changes were detected in retinitis pigmentosa in CRB1, GUCY2D, and RPGRIP1; and in LCA patients in CRB1, GUCY2D, and RPE65. These data, combined with previous reports, suggest that LCA and juvenile ARRP are closely related and belong to a continuous spectrum of juvenile retinitis pigmentosa.

Kearns-Sayre syndrome with a phenocopy of choroideremia instead of pigmentary retinopathy.

Mitochondrial DNA (mtDNA) was deleted in a patient with Kearns-Sayre syndrome (KSS) presenting with a choroideremia-like fundus picture instead of pigmentary retinopathy. No evidence for X-linked choroideremia was present, and because of the strong association between KSS and deleted mtDNA, we suggest that choroideremia is a phenocopy and can be part of KSS.

Further delineation of the acro-renal-ocular syndrome.

A triad of acral, renal, and ocular abnormalities was reported previously in four families. We report on a fifth family, in which a mother, one of her four sons and one of her two daughters are affected. Major findings in the acro-renal-ocular syndrome are upper limb abnormalities, mainly thumb hypoplasia, eye abnormalities such as coloboma and Duane anomaly and renal migration defects. A close embryological-temporal relationship between the traits of this entity suggest a common monogenic cause. The pattern of inheritance is probably autosomal dominant. Because of a wide variability of clinical manifestations, recognition of the syndrome in individual cases may be difficult.

Autosomal recessive retinitis pigmentosa with preserved para-arteriolar retinal pigment epithelium.

Retinitis pigmentosa with preserved para-arteriolar retinal pigment epithelium is a rare form of retinitis pigmentosa that starts early in life with preservation of retinal pigment epithelium adjacent to and under the retinal arterioles and that has hitherto been described as an isolated form. We examined 22 patients from one large family, together with two isolated patients, and confirmed the presumed autosomal recessive mode of inheritance in this type of retinitis pigmentosa. New findings associated with retinitis pigmentosa with preserved para-arteriolar retinal pigment epithelium were asteroid hyalosis in four (17%) of 24 patients, tortuosity of retinal arterioles in 11 (46%) of 24 patients, peripheral regions of opacified vessels in eight (33%) of 24 patients, and preservation not only of the para-arteriolar pigment epithelium, but also of the peripheral retinal pigment epithelium in 13 (54%) of 24 patients. Previously reported signs present in these patients were nystagmus in six (25%) of 24 patients, hypermetropia in 23 (96%) of 24 patients, optic nerve head drusen in nine (38%) of 24 patients, vascular sheathing in 11 (46%) of 24 patients, maculopathy in all 24 patients (100%), yellow round deposits in the posterior pole in nine (38%) of 24 patients, exudates resembling those in Coats' disease in two (8%) of 24 patients, visual field defects in all 24 patients (100%), and nondeductible electroretinograms in 21 (91%) of 23 patients. Linkage analysis carried out in the large family resulted in the assignment of a gene for retinitis pigmentosa with preserved para-arteriolar retinal pigment epithelium to chromosome 1q31-q32.1.

Thr4Lys rhodopsin mutation is associated with autosomal dominant retinitis pigmentosa of the cone-rod type in a small Dutch family.

A mother and daughter with autosomal dominant retinitis pigmentosa (adRP) were found to carry a cytosine-to-adenine transversion mutation at codon 4 of the rhodopsin gene. This mutation predicts a substitution of lysine for threonine at one of the glycosylation sites in the rhodopsin molecule (Thr4Lys). Both patients presented with a similar phenotype including a tigroid pattern of the posterior pole and a regional predilection for degenerative pigmentary changes in the inferior retina with corresponding visual field defects. The electroretinographic pattern was suggestive of RP of the cone-rod type. This report documents the clinical findings associated with this defined mutation of the rhodopsin gene.

Dominant cone dystrophy starting with blue cone involvement.

The results of ophthalmological and colour vision studies are reported on 13 patients from a family with a dominant cone dystrophy spanning seven generations. The onset of visual deterioration occurred in the third or fourth decade. In the early stages of the disease, when visual acuity is still close to normal, a severe defect in the blue sensitivity is already present, as measured by spectral sensitivity curves and other tests suitable for the detection of tritan defects. In our opinion this condition represents a distinct entity with autosomal dominant inheritance.

Efficient DNA carrier detection in X linked juvenile retinoschisis.

Juvenile retinoschisis is a rare, X linked hereditary vitroretinal degeneration. Female carriers of the disease do not develop any ocular abnormalities. Therefore, carrier detection by DNA analysis is extremely useful for these females. In order to evaluate the usefulness of a new class of DNA markers for carrier detection in X linked juvenile retinoschisis, DNA carrier detection or carrier exclusion was carried out in four possible carriers for X linked juvenile retinoschisis. The use of these highly polymorphic CA repeats, closely linked to the RS gene, greatly enhances both the reliability and feasibility of carrier detection in X linked juvenile retinoschisis.

Grid laser photocoagulation for macular oedema in uveitis or the Irvine-Gass syndrome.

AIMS: To determine the effect of modified macular grid photocoagulation in patients with refractory macular oedema due to uveitis or cataract extraction. METHODS: In this study 20 patients with macular oedema underwent modified macular grid laser photocoagulation and were followed by means of standardised examinations (day 0, months 2, 6, and 12) consisting of best corrected visual acuity and fluorescein angiography. RESULTS: The mean visual acuity increased from 0.16 before to 0.3 after laser treatment (p = 0.013), and fluorescein leakage was significantly reduced (p = 0.005). Visual prognosis was influenced by duration of the uveitis, not by sex or age. CONCLUSION: Modified macular grid laser photocoagulation had a beneficial effect on macular oedema caused by uveitis or the Irvine-Gass syndrome. A prospective, randomised study is needed to determine the exact place of modified macular grid photocoagulation in the treatment of patients with inflammatory or postsurgical macular oedema.

Long term ocular and neurological involvement in severe congenital toxoplasmosis.

AIMS: This study was set up to determine the long term ocular and systemic sequelae in patients with severe congenital toxoplasmosis. METHODS: Cross sectional and retrospective study of 17 patients with severe congenital toxoplasmosis. RESULTS: In addition to chorioretinitis (100%), the most common abnormal ocular features were optic nerve atrophy (83%), visual acuity of less than 0.1 (85%), strabismus, and microphthalmos. In 50% of cases we observed iridic abnormalities and about 40% developed a cataract. Overt endocrinological disease, diagnosed in five of 15 patients, included panhypopituitarism (n = 2), gonadal failure with dwarfism (n = 1), precocious puberty with dwarfism and thyroid deficiency (n = 1), and diabetes mellitus and thyroid deficiency (n = 1). The observed endocrinological involvement was associated in all cases with obstructive hydrocephalus with a dilated third ventricle and optic nerve atrophy. CONCLUSION: The recognition of long term ocular, neurological, and endocrinological sequelae of congenital toxoplasmosis is important for medical management of these severely handicapped patients.

A new autosomal dominant vascular retinopathy syndrome.

We describe a new syndrome with autosomal dominant transmission whose most striking feature is vascular retinopathy. The retinopathy is often associated with migraine, Raynaud's phenomenon and mental changes, mainly forgetfulness, aggression and depression. To define this syndrome we collected medical data on 110 family members. General ophthalmological examination and fluorescein angiography were performed in 61 persons. The retinopathy, as diagnosed in 22 persons, is characterized by central and peripheral microangiopathy, areas of capillary non-perfusion, haemorrhages, cotton wool spots and, in a more advanced stage, occlusion of large retinal vessels, which can induce a neovascular response. A vascular occlusive disorder may be the common aetiological factor of the various manifestation of this syndrome.

Cataracts, radiculomegaly, septal heart defects and hearing loss in two unrelated adult females with normal intelligence and similar facial appearance: confirmation of a syndrome?

Two unrelated, adult females with normal intelligence are described. They show a similar clinical picture with a long and narrow face, congenital cataract, microphthalmia, microcornea, a high nasal bridge, a short nose, a broad nasal tip, a long philtrum, bilateral hearing loss, persistent primary teeth, oligodontia, variable root length including dental radiculomegaly, heart defects and cutaneous syndactyly of the 2nd-3rd toes. Abnormalities present in only one of the two patients were a cleft palate and a transverse vaginal septum, respectively. There are numerous similarities between our two patients and the family described by Wilkie et al. ((1993): Clin Dysmorphol 2: 114-119) and all may be examples of the same entity.

The Peters'-Plus syndrome: description of 16 patients and review of the literature.

Peters'-Plus syndrome is characterized by Peters' anomaly, a typical face, cleft lip and palate, short limb dwarfism, and developmental retardation. We report the follow-up of six patients in the original report, 10 yet unreported patients, and review 26 patients that have been reported in the literature. The spectrum of the syndrome is broadened by data from affected sibs which indicate that a wider range of anterior chamber cleavage disorders may be present, a cleft lip or palate need not be present, and developmental retardation may be mild or even absent. An increased foetal loss in families with Peters'-Plus syndrome may indicate intrauterine death of some foetuses affected by the syndrome. The pattern of inheritance is autosomal recessive.

Incidence of retinopathy of prematurity over the last decade in the Central Netherlands.

BACKGROUND AND OBJECTIVES: To retrospectively analyze changes in incidence and risk factors of retinopathy of prematurity (ROP) over two periods, 10 years apart, in the central Netherlands. METHODS: Data of 570 infants admitted between 2001 and 2005, screened for ROP according to the Dutch National guideline, were compared to those of 538 infants admitted between 1991 and 1995. RESULTS: Incidence of ROP decreased significantly over the last decade (40.9% in 1991-1995 vs. 23.3% in 2001-2005, p < 0.001), together with incidence of severe ROP (stage >or=3) (3.3 vs. 1.2%, p < 0.05). In infants with a birth weight (BW) <1,000 g incidence of ROP dropped significantly (67.0 vs. 41.8%, p < 0.001), as well as incidence of severe ROP (8.1 vs. 3.0%, p < 0.05). For infants with a BW >or=1,000 g incidence of ROP also declined significantly (27.1 vs. 13.0%, p < 0.001), that of severe ROP remained unchanged (0.8 vs. 0.3%). In both periods gestational age, duration of artificial ventilation, small for gestational age (SGA) and postnatal steroids were independent risk factors for ROP. CONCLUSIONS: In the central Netherlands, incidence of ROP and severe ROP has significantly decreased, also in infants with BW <1,000 g. Risk factors remained unchanged.

Pigmented paravenous retinochoroidal atrophy: a nosologic entity?

A new case of pigmented paravenous retinochoroidal atrophy is described. Besides the characteristic fundus picture, this 21-year-old male showed a remarkable difference in retinal function between the two eyes, the function of the left eye being much more impaired. This might suggest a progressive condition, in which the right eye lags behind. In addition this patient had a vitreoretinal degeneration resulting in five peripheral retinal tears in the right eye.