Intrafamilial phenotypic variability in families with RDS mutations: exclusion of ROM1 as a genetic modifier for those with retinitis pigmentosa.

OBJECTIVES: To identify suspected RDS mutations in families in which different people have been identified with either generalised retinal dystrophy or macular dystrophy. METHODS: Two families with a retinal dystrophy were extensively phenotyped and blood was taken for mutation analysis of the RDS (all) and ROM1 (retinitis pigmentosa patients only) genes. RESULTS: A novel p.Trp94X mutation in RDS was found in all three affected members of a two-generation family that was associated with retinitis pigmentosa in the son, pattern dystrophy in the daughter and fundus flavimaculatus in the mother. In the second family, the proband with retinitis pigmentosa carried a p.Arg220Trp mutation. The mother, who was unavailable for mutation screening, had adult vitelliform macular dystrophy. No ROM1 mutations were found in those with retinitis pigmentosa in either family. CONCLUSION: Mutations in RDS can be associated with an intrafamilial variation in retinal disease. The phenotypes range from Stargardt-like macular dystrophy to classic retinitis pigmentosa. CLINICAL RELEVANCE: Intrafamilial phenotypic variation may be due to the presence of environmental or genetic modifying factors. The presence of a modifying-sequence change in the coding region of ROM1 for two people with retinitis pigmentosa from two families with intrafamilial variation in RDS mutation phenotype has been excluded in this study.

Photodynamic therapy with verteporfin in Belgian patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration.

This is a retrospective, uncontrolled study of 55 patients (61 eyes) treated between January 2002 and January 2004 with Photodynamic Therapy with Verteporfin for subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration. The eyes were divided into three groups: predominantly classic CNV (21 eyes), minimally classic CNV (7) and occult with no classic CNV (4 eyes). For 31 patients (32 eyes) the follow-up period was at least one year. The following parameters were studied: visual acuity, progression of the CNV, and activity of the CNV expressed as leakage on fluorescein angiography and edema on OCT. In the group of predominantly classic CNV at 12 month the treatment resulted in an inactive lesion in 43% of the eyes, however in 48% the visual acuity had decreased. For the group of minimally classic CNV, regression of activity was noted in 71% but vision further decreased in 57%. In the group of occult with no classic CNV one eye developed classic CNV, whereas the lesion regressed on 3 eyes. Two of the 4 eyes lost vision. These results suggest that although PDT is capable of stabilizing the lesion, further visual loss is to be expected in a large number of patients.

Iatrogenic ocular vascular occlusions: case reports.

Report of two patients with severe loss of visual acuity after surgery in the head and neck area. Ophthalmic examination and imaging studies demonstrate an occlusion of the ophthalmic and central retinal arteries. In both cases, the underlying physiopathology is the embolisation by an intra-operatively injected substance. Embolisation is thought to occur via anastomosing branches between the external and internal carotid arteries. These cases demonstrate that surgery in head and neck area can result in unexpected and devastating ocular complications.

Myopia: more than a refractive error--LASIK and retinal dystrophies.

Three patients who had undergone laser in situ keratomileusis (LASIK) correction for myopia were first seen because of suboptimal visual acuity (VA) and night blindness and/or photophobia. After a comprehensive examination including psychophysical and electrophysiological tests, two of the three patients were shown to suffer from a progressive conerod dystrophy. The third patient had retinitis pigmentosa. These cases illustrate the need for in depth preoperative evaluation in myopic patients about to undergo LASIK when signs or problems of night blindness and/or photophobia are present.

Effect of alpha-1 and beta agonists on contraction of bovine retinal resistance arteries in vitro.

Contractile responses of bovine retinal arteries (BRA) (diameter: 179 +/- 9 micron, n = 25) to high K+, circumferential stretch and adrenergic stimulation were studied in vitro. BRA could be activated by rapid circumferential stretch. Under resting conditions, phenylephrine consistently activated BRA at the highest dose of the drug used (10(-5) M). During K+- and stretch-induced activation, significant contractile responses to phenylephrine appeared at lower doses (respectively, 3.10(-8) and 10(-6) M). Isoproterenol did not relax K+- and stretch-induced contractions. Therefore, (1) BRA probably can autoregulate through a myogenic mechanism on the basis of stretch; (2) during alpha 1 adrenergic stimulation, myogenic autoregulatory responses probably increase; (3) contractile responses to alpha 1 adrenergic stimulation are masked under resting conditions; and (4) BRA may not possess functional beta adrenergic receptors.

Effects of beta-antagonists on contraction of bovine retinal microarteries in vitro.

Contractile responses of bovine retinal microarteries (BRA) (diameter: 198 +/- 5 microns, n = 49) to beta-antagonists, local anesthetics and Ca2(+)-antagonists were studied in vitro. Propranolol (10(-8)-10(-5) M) relaxed K(+)-activated BRA dose-dependently, whereas timolol (10(-8)-10(-5) M) relaxed K(+)-activated BRA only weakly at the highest doses. The relaxation by propranolol was not mediated through interaction with adrenergic nerve endings, since fluorescence histochemistry showed absence of such nerve endings in BRA. In addition, propranolol still relaxed BRA which were treated with 6-hydroxydopamine (6-OHDA), which causes chemical adrenergic denervation. Local anesthetic properties of propranolol had no part in the relaxation: lidocaine (10(-7)-10(-5) M) did not relax K(+)-activated BRA. Verapamil (10(-9)-10(-6) M) relaxed K(+)-activated BRA markedly and dose-dependently. Both verapamil and propranolol relaxed phasic K(+)-induced force more than tonic force. By contrast, they relaxed only the tonic part of serotonin-induced force, and they had no effect on stretch-induced active force. Therefore: 1) propranolol dilates BRA more than does timolol, possibly because of the Ca2(+)-antagonistic properties of the former; 2) beta- and Ca2(+)-antagonists probably spare myogenic autoregulation of blood flow and do not prevent, but could partially reverse, serotonin-induced arterial spasm.

Waardenburg syndrome, Hirschsprung megacolon, and Marcus Gunn ptosis.

A patient with Waardenburg syndrome type II associated with Hirschsprung megacolon and Marcus Gunn ptosis is presented. It is suggested that these different anomalies are manifestations of the same neurocrestopathy.

Pseudoxanthoma elasticum: similar autosomal recessive subtype in Belgian and Afrikaner families.

A multidisciplinary survey of the clinical and genetic characteristics of 26 Belgian and 32 Afrikaner families with biopsy-proven pseudoxanthoma elasticum (PXE) was undertaken. The major PXE phenotype emerging from this study is very similar in both patient groups and is characterized by severe ophthalmologic manifestations with variable, mild cutaneous and vascular symptoms. In the families with more than one affected relative, segregation analysis is compatible with autosomal recessive inheritance in both groups. It is suggested that the PXE phenotype of these Belgian and Afrikaner patients is distinct from the other recognized PXE subtypes. The phenotypic resemblance in both patient groups raises the question whether a similar genetic mechanism is involved.

Electrophysiologic studies in birdshot chorioretinopathy.

We investigated retinal function in 16 patients with birdshot chorioretinopathy. Consistent abnormalities of dark adaptation, color vision, visual field, electro-oculography, electroretinography, and visual-evoked cortical potentials were found. They included raised thresholds of dark adaptation, acquired dyschromatopsia, mainly of the blue-yellow type, an electroretinogram with reduced amplitude, increased latency of the b-wave and absent oscillatory potentials, an abnormal electro-oculogram, and in many a marked disturbance in the pattern reversal visual-evoked cortical potential. The a-wave of the electroretinogram, the fast oscillations of the standing potential, and the flash visual-evoked cortical potential were well preserved. The nature of the abnormalities suggests that dysfunction was caused by inner retinal disease. Little evidence indicated outer retinal dysfunction resulting from choroidal inflammation.

Neovascularization after argon laser photocoagulation of macular lesions.

In three patients treated for macular degeneration with argon laser photocoagulation choroidal neovascularization occurred four to six weeks later at the photocoagulation site. Two of the patients were treated for angioid streaks of the macular region, the third patient was treated for disciform macular degeneration. Argon laser photocoagulation also induced neovascularization experimentally in pigmented rabbits.

HLA typing in birdshot chorioretinopathy.

We examined 49 patients with birdshot chorioretinopathy in whom HLA typing had been performed. Of these 49 patients, 47 (95.9%) had the HLA-A29 antigen. The HLA-B12 (B44) antigen was also significantly associated with the disease, but this antigen is known to be in linkage disequilibrium with the antigen HLA-A29. The HLA-A2 antigen was less frequent in patients with birdshot chorioretinopathy than in the control group of normal European individuals (20% as compared to 44.6%).

Subtraction ICG angiography in Harada's disease.

BACKGROUND/AIM: The significance of indocyanine green (ICG) angiography (ICGA) in Harada's disease still awaits clarification in many respects. This study investigates the details of choroidal lesions observed in Harada's disease by the subtraction method. METHODS: Eight patients with Harada's disease were followed with ICGA. ICG angiograms were obtained with a Topcon high resolution digital fundus camera and processed with a Topcon IMAGEnet computer system. Image subtraction was conducted for analysing serial angiograms taken at about 2 second intervals during the dye transit phase and those taken in the early and middle phases of angiography. RESULTS: Standard ICG images of acute stage disease showed delayed choroidal filling in the early phase. Mid phase angiograms showed areas with bright fluorescence of variable intensity, indicating intrachoroidal ICG leakage. With image subtraction of angiograms with an interval of seconds the choroidal vessels could be imaged sequentially, with the choroidal arteries visualised first, followed by the definition of the choriocapillaris and then the choroidal veins. The choroidal veins with delayed filling were visualised as positive images in serial subtraction angiograms. Subtraction with an interval of minutes showed uneven background fluorescence and bright fluorescence corresponding to the areas of intrachoroidal ICG leakage. After the disease subsided with steroid therapy, angiography revealed an improvement in delayed choroidal filling. Image subtraction by the second allowed a clear visualisation of improved choroidal venous filling, while subtraction by the minute showed homogeneous background fluorescence, eliminating brighter areas. CONCLUSION: Subtraction ICGA demonstrated that delayed filling of the choroidal veins of varying severity occurs in association with hyperpermeability of the choroidal vessels in the course of Harada's disease.

Ocular non-Hodgkin's lymphoma: a clinical study of nine cases.

BACKGROUND: Primary oculocerebral large cell malignant non-Hodgkin's lymphoma, formerly called ocular reticulum cell sarcoma, runs a uniformly fatal course. Once the central nervous system (CNS) is involved, survival without treatment is very limited. Although treatment does not substantially improve the long term survival, it provides short term improvement in these patients. METHODS: The charts of all patients with ocular involvement of non-Hodgkin's lymphoma followed during the period 1984-93 were reviewed. The diagnosis of non-Hodgkin's lymphoma was made by different diagnostic approaches: CNS biopsy, anterior chamber tap, vitrectomy, haematology, and necropsy. RESULTS: Eight patients had oculocerebral large cell and one had small cell non-Hodgkin's lymphoma. Five patients with pure ocular localisation had initially received steroid treatment for intermediate uveitis. First diagnosis was made on CNS biopsy in three, anterior chamber tap in one, vitreous aspirate in three, haematology in one, and necropsy in one case. CONCLUSION: Ocular non-Hodgkin's lymphoma is a difficult diagnosis. Vitrectomy allows cytological diagnosis in most but not all cases. When no treatment is given, patients survive for only a few weeks once the CNS is involved. Although the disease is eventually fatal, treatment by means of radiotherapy, steroid administration, and vitrectomy can allow these patients to lead a normal professional and social life during the years between recurrences.

Clinicopathological correlation in exudative age related macular degeneration: histological differentiation between classic and occult choroidal neovascularisation.

AIMS: To analyse the histopathology of classic and occult choroidal neovascular membrane surgical specimens in age related macular degeneration. METHODS: 35 membranes, from a consecutive series of surgically removed choroidal neovascular membranes in age related macular degeneration, were classified as classic or occult following the guidelines of the Macular Photocoagulation Study. Membranes with classic as well as occult components were considered as mixed membranes. The membranes were serially sectioned and stained with haematoxylin and eosin, Masson trichrome, periodic acid-Schiff, and phosphotungstic acid haematoxylin stain. The correlation has been made in a masked fashion. RESULTS: 31 membranes (19 classic, 10 occult, and two mixed membranes) could be analysed histologically. 18 classic choroidal neovascular membranes had a major subretinal fibrovascular component and 10 of these had an additional, minor fibrovascular component under the retinal pigment epithelium. The 10 occult membranes contained a fibrovascular component under the retinal pigment epithelium and the two mixed membranes contained fibrovascular tissue on both sides of the retinal pigment epithelium. Fibrin and remains of outer segments tended to occur at the lateral edges of classic membranes and to cover the inner surface of occult membranes. CONCLUSION: Classic choroidal neovascularisation in age related macular degeneration is predominantly composed of subretinal fibrovascular tissue while occult choroidal neovascularisation is composed of fibrovascular tissue at the choroidal side of the retinal pigment epithelium.

Retinal manifestations in fibromuscular dysplasia.

Fibromuscular dysplasia of the arteries (FMD) is a segmental angiopathy which may produce obstruction of the carotid, cerebral, renal, mesenteric, coronary or iliac arteries. Except for lesions related to arterial hypertension, retinal manifestations have not yet been reported. This paper describes the case of a 10-year-old boy with progressive deafness, a history of an unexplained stroke and progressive occlusions of the retinal arterioles in the fundus periphery. This resulted in retinal neovascularization and recurrent retinal and vitreous hemorrhages. Despite repeated photo- and cryocoagulation the eyes progressed to a tractional retinal detachment which was successfully treated by vitrectomy and scleral buckling. The diagnosis of FMD was made on the basis of a histopathological examination of a temporal artery biopsy. The child also presented an asymptomatic but severe aneurysmal dilatation of the aorta and CT scan and MRI showed dilated cerebral arteries. The father of our patient had died at the age of 27 years either from myocardial infarction or rupture of a dissecting aortic aneurysm. He was highly myopic and had lost one eye from retinal detachment. The younger brother of our patient also presents aneurysmal dilatation of the aorta and tortuous cerebral vessels. Ocular examination is still normal. The findings in this family are compatible with an autosomal dominant inheritance with variable expression.

Clinical application of indocyanine green angiography to choroidal neovascularization.

In order to evaluate the clinical usefulness of indocyanine green video-angiography (IA), the angiographic features of choroidal neovascular membranes (CNM) were investigated in 27 eyes with choroidal neovascular diseases by means of standard fluorescein angiography (FA) and IA. FA showed the existence of CNM in 21 eyes and IA demonstrated evidence of CNM in 19 eyes, as "fan, comb or spotty hyperfluorescence" in the early stage and "leakage" in the late stage. In 6 out of 19 eyes the existence of CNM was shown by IA, while FA failed to identify the precise location and size of CNM due to the masking effect of overlying turbid fluid, massive hemorrhage or a large amount of serous fluid. The results imply that IA has an advantage over FA in cases where FA shows only the sign of occult choroidal neovascularization, and that IA can be applied to neovascular maculopathy as a routine examination.

Anaesthesia for fluorescein angiography of the ocular fundus in the miniature pig.

A safe and reproducible procedure is described for anaesthesia and ophthalmic fluorescein angiography in the miniature pig. Twenty examinations were performed in five adult miniature pigs. A detailed description is given of the anaesthetic procedure, in particular of the techniques for endotracheal intubation and for intra-arterial and intravenous cannulation. All cardiovascular parameters recorded during the experiments remained within acceptable anaesthetic limits. The fluorescein angiographic technique, which is routinely used in human ophthalmology, was adapted for the pig. This procedure for in vivo examination of the porcine eye is interesting and useful for experimental ophthalmic research.

Diagnosis and differential diagnosis of malignant melanomas of the choroid.

A complete ocular examination is essential for the correct diagnosis of a malignant melanoma of the choroid. The single, most important technique is indirect ophthalmoscopy associated with biomicroscopy of the fundus. Fluorescein angiography may provide additional arguments for malignancy, but with this method it is not always possible to differentiate a malignant melanoma from a suspected naevus or even a choroidal metastasis. Fluorescein angiography provides however a detailed and objective document which allows a better follow-up of suspected lesions. As with infrared angiography, choroidal vessels are more readily seen, this technique may prove to be of diagnostic importance. A- and B-scan ultrasonography are essential to precisely measure a choroidal lesion. Especially A-scan may also allow tissue differentiation. Diaphanoscopy is especially useful in the diagnosis of choroidal haemangioma. Even naevi may provide relative or absolute scotomas. The diagnostic importance of perimetry is therefore very limited. CT-scan and especially MRI are helpful in detecting extra-ocular extension. In case of atypical naevi, a close observation for potential growth is advised. Malignant melanomas of the choroid have to be differentiated from other fundus tumours, but also from inflammatory and degenerative conditions.

Flecked retina disorders.

This survey describes a number of fundus conditions characterized by flecks in the retina. The term "flecked retina" was introduced by Krill and Klien to describe fundus conditions characterized by multiple yellowish-white lesions of various size and configuration, without vascular or optic nerve abnormalities. Originally this group consisted of four diseases: fundus albipunctatus, fundus flavimaculatus, familial drusen and fleck retina of Kandori. However, far more diseases correspond to the rather vague definition, including primary hereditary ocular diseases such as retinitis punctata albescens or Bietti's crystalline dystrophy, neuro-ophthalmologic syndromes such as Kjellin's syndrome, secundary retinal flecks due to metabolic disorders such as Alport's syndrome, cystinosis, oxalosis or membrano-proliferative glomerulonephritis, iatrogenic retinopathy due to Tamoxifen or Canthaxanthin and carential diseases such as vitamin A deficiency. The precise diagnosis is not only based on the close observation of the fundus, but demands often extensive psychophysical examination of the patient and sometimes of his family.

[Placoid epitheliopathy and serpiginous choroidopathy]. / Epithéliopathie en plaques et choroïdopathie serpigineuse.

Both acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and geographic or serpiginous choroiditis are probably the result of a primarily inflammatory involvement of the choroid. In the acute phase both diseases may present a similar appearance. The evolution is however quite different. APMPPE usually affects younger individuals and is almost always bilateral; both eyes are often affected simultaneously. In geographic choroiditis the second eye is sometimes involved weeks up to years after the first eye. APMPPE may be considered as the ocular manifestation of a systemic disease possibly induced by a viral infection. The etiology of geographic choroiditis is still unknown.