Subretinal fibrosis is associated with fundus pulverulentus in pseudoxanthoma elasticum.

BACKGROUND: Pseudoxanthoma elasticum (PXE) is a rare autosomal recessive disorder caused by mutations in the ABCC6 gene, resulting in various retinal lesions, among other systemic manifestations. Visual loss may occur in PXE, most commonly caused by choroidal neovascularization and macular atrophy, but little is known about the consequences of fundus pulverulentus (FP) in PXE. The aim of this study was to evaluate ophthalmic outcomes in patients with FP associated with PXE in a large series of PXE patients. METHODS: In a retrospective observational study, ophthalmic outcomes were compared between two groups of age-matched patients with genetically and pathologically confirmed PXE: one group with FP versus one without FP. All included patients underwent thorough clinical examination. Further investigation (optical coherence tomography (OCT), Cirrhus, Zeiss Germany, and/or fluorescein/indocyanin green angiography) was performed in cases of suspected choroidal neovascularization (CNV). RESULTS: The study included 13 PXE patients with FP (group 1: 8 men and 5 women, aged 45-65 years) and 47 age-matched PXE patients without FP (group 2: 19 men and 28 women). Mean patient follow-up was 63 months (range 0-132 months). Subretinal fibrosis (SRF) was more frequently associated with FP (9/26 eyes, 34.6%), compared to absence of FP (4/94, 4.2%) (p = 0.0001). Independently of SRF, FP can evolve into deep macular atrophy and/or CNV with dramatic consequences for central vision. CONCLUSIONS: Fundus pulverulentus may occur in PXE and is most commonly associated with subretinal fibrosis in the posterior pole and visual loss by macular atrophy even in the absence of CNV.

Carotid rete mirabile and pseudoxanthoma elasticum: an accidental association?

We report the case of a young female patient with a transient amaurosis due to a carotid rete mirabile (CRM), a rare congenital carotid malformation, and pseudoxanthoma elasticum (PXE), an inherited autosomal recessive systemic metabolic disorder characterised by fragmentation and mineralisation of elastic fibres in connective tissues (skin, eyes) and the vascular system. CRM is a rare form of intracranial carotid malformation whose association with PXE (6 cases at present) would appear not to be accidental. This observation suggests a new link between congenital arterial remodelling and the PXE.

A study of optic nerve head drusen in 38 pseudoxanthoma elasticum (PXE) patients (64 eyes). Location of optic nerve head drusen in PXE.

PURPOSE: To investigate the prevalence and location of optic nerve head drusen and their potential association with other PXE-related ophthalmic abnormalities. MATERIALS AND METHODS: Thirty-eight of the 155 patients (57 male and 98 female aged 49±17 years) included in this retrospective study had optic nerve head drusen. All of the patients underwent a comprehensive ophthalmic examination, including color images using red-free, blue and red filters, autofluorescence imaging and late-phase ICG frames. Comparative analysis of both groups (optic nerve head drusen or not) was conducted using R statistical software. RESULTS: The prevalence of optic nerve head drusen in our cohort was 24.5%. In this study, no evidence of a significant link between optic nerve head drusen and other fundus abnormalities was detected. They were more commonly located in the nasal sector than in the temporal sector of the optic disc (P<0.001). They were more frequently situated superonasally than inferonasally (P<0.004), superotemporally (P<0.001) or inferotemporally (P<0.03). No central visual field defect was observed in OND+ patients who were unaffected by macular disorders. DISCUSSION: We hypothesized this predominantly nasal primary location may result from greater sensitivity in the nasal optic nerve fibers which follow a much more angular path once they arrive in the scleral canal, accounting for accumulation of axoplasmic debris. CONCLUSION: In PXE, optic nerve head drusen are mostly located in the superonasal quadrant, causing progressive optic nerve invasion but probably no central visual field defects.

[Study of fundus examination by age in 158 pseudoxanthoma elasticum patients]. / Étude du fond d'œil en fonction de l'âge dans le pseudoxanthome élastique chez 158 patients.

PURPOSE: To study the prevalence of fundus anomalies among patients with pseudoxanthoma elasticum as a function of their age. MATERIAL AND METHODS: All patients have had a complete ophthalmologic examination in multidisciplinary consultation for PXE in a national reference center. RESULTS: Hundred and fifty-eight patients (60 men and 98 women aged from 10 to 90 years old, mean 45±17 years) were included in a cross-sectional retrospective study. All fundus pictures were retrospectively reviewed over 9 years. Peau d'orange (55.6 %), was the first fundus feature observed in younger patients and disappeared with age. Angioid streaks (100 %), appeared during the second decade of life: at first hypofluorescent and then hyperfluorescent after 40 years old. Crystalline bodies (54.1 %), optic nerve head drusen (19 %) and peripheral pigmentation (39.9 %) were found in the various age groups. Macular atrophy (33.5 %) could have resulted from subretinal neovascularization (40.8 %), pattern dystrophies (7.9 %) or subretinal fibrosis (5.3 %). The onset of neovascularization appeared during the fourth decade. DISCUSSION: Progressive centrifugal calcification of Bruch's membrane is the cause of the many fundus features observed in PXE patients. CONCLUSION: Knowledge of the natural history of PXE can help the clinician explain and reassure patients about the evolving risks of ophthalmological involvement, particularly the fact that neovascular complications arise from the fourth decade.

[Treatment with ranibizumab for choroidal neovascularization secondary to a pseudoxanthoma elasticum: Results of the French observational study PiXEL]. / Traitement par ranibizumab des néovascularisations choroïdiennes secondaires à un pseudoxanthome élastique : résultats de l'étude observationnelle française PiXEL.

INTRODUCTION: Pseudoxanthoma elasticum (PXE), a rare hereditary connective tissue disorder, may be complicated by angioid streaks (AS) and choroidal neovascularization (CNV), which may lead to irreversible loss of visual acuity (VA). Here we describe the safety and efficacy of ranibizumab in patients with CNV secondary to PXE. METHODS: A multicenter (n=23), observational study of a retrospective/prospective cohort, performed under real world conditions in France in all patients with CNV secondary to PXE who received at least one ranibizumab injection as of October 2011. The study objectives were to describe the mean annual number and reason for ranibizumab injections since initiation, evolution of best-corrected visual acuity (BCVA by Early Treatment Diabetic Retinopathy Study [ETDRS] letters), and safety. RESULTS: Patients (n=72; 98 eyes) had a mean age of 59.6±8.3years and consisted of 54.2% men. The criterion for retreatment was based mainly on loss of VA, progression of CNV and angiographic leakage. CNV was primarily subfoveal or juxtafoveal (73.4%), and the initial mean VA was 64.6 ETDRS letters. On average, visual acuity of all eyes analyzed was relatively stable during the 2-year follow-up (62.3 letters vs 64.6 letters at the first injection), and 88.6% of eyes maintained VA between -15 and +15 letters or gained over 15 letters. No deaths or new intolerances were described. CONCLUSIONS: These results showed that ranibizumab was able to maintain stable VA in clinical practice for at least 2years in patients with CNV secondary to PXE, and to significantly reduce the frequency of neovascularization relapses, with a limited number of injections. The treatment was well tolerated by the patients.

Proliferative retinopathy in patients with type 1 diabetes of less than 5 years' duration.

The position statement about diabetic retinopathy postulates that at least 3-5 years of duration of diabetes are needed for the retinopathy to occur, and initial retinal examination should be performed within 3-5 years after the initial diagnosis. We report here the case of a 18 year-old type 1 diabetic woman with a proliferative retinopathy discovered 2 years after the onset of a clinical diabetes. The hypothesis of a Latent Autoimmun Diabetes in Adults (LADA) could not be excluded and we propose, particularly in this context, to detect a diabetic retinopathy at the onset of diabetes.

Description of microangiopathy in children with type 1 diabetes mellitus: a 19-year retrospective study.

BACKGROUND: The aim of the study was to estimate the outcome of patients with type 1 diabetes followed in a university hospital in the paediatric department and then in the adult diabetic department for at least 10 years. METHODS: We made a retrospective analysis of 50 patients (28 women and 22 men) with type 1 diabetes with disease duration of 19 +/- 6 years and analysed whether retinopathy and nephropathy had progressed, had remained unchanged or had improved or normalised. RESULTS: The mean age of diabetes onset was 8 +/- 4 years (1-16). Ketoacidosis revealed diabetes in 36% of the children. Mean HbA(1c) was 8.6 +/- 1.8%, and was over 8.5% in 34% of the patients. The mean age at onset of puberty (Tanner stage II) was 12 +/- 1 years in girls and 13 +/- 1 years in boys. Mean HbA(1c) was 7.9 +/- 1.2% during the year before onset of puberty and 8.7 +/- 1.1% in the following 3 years, corresponding to a 10% pubertal increase in HbA(1c). Retinopathy was seen in 50% of the patients at a mean age of 22 +/- 5 years, 15 +/- 6 years after onset of diabetes. Mean HbA(1c) was 9.7 +/- 1.6% in patients with proliferative retinopathy, 9.0 +/- 1.5% in patients with non proliferative retinopathy, and 8.1 +/- 1.3% in those without (p=0.02, proliferative versus no retinopathy, p > 0.05 non proliferative versus no retinopathy). Microalbuminuria was diagnosed in 26% of the patients. Mean HbA(1c) was 9.3 +/- 2.1% in patients with microalbuminuria versus 8.1 +/- 1.3% in those with normoalbuminuria (p=0.02). CONCLUSIONS: Glycemic control was similar in patients with non proliferative retinopathy and those without. Proliferative retinopathy and nephropathy were both related to the level of glycemic control.

[Congenital ectropion of the iris epithelium and glaucoma]. / Ectropion congénital de l'épithélium irien et glaucome.

Two cases of unilateral ectropion uveae with ipsilateral juvenile glaucoma are reported including one with ipsilateral ptosis. This rare, non progressive anomaly, is characterized by the presence of iris pigment epithelium on the anterior surface of iris stroma, quite often associated with neurofibromatosis, ipsilateral ptosis or Rieger's syndrome. Congenital or juvenile glaucoma is almost systematically associated with the condition and must be evaluated and treated. Pathogeny of the anomaly has to be interpreted keeping in mind the concept of neurocristopathy, i.e. developmental anomalies of neural crest origin tissues.

[Routine monitoring of patients treated with synthetic antimalarials]. / Surveillance pratique des malades traités par anti-paludéens de synthèse.

Routine tests of visual acuity, and ocular fundus, angiography, and ERG examinations should be conducted regularly in patients receiving synthetic antimalarial drugs. Toxicity of these compounds is a current problem as 8 out of 81 patients being treated presented symptoms associated with ERG changes or macular lesions, and reduced visual acuity in some cases. There was a lack of correlation between ERG effects and the onset of macular disorders: one patient had marked macular changes and a normal ERG while another had a normal fundus and visual acuity but abolished ERG activity. Identical doses do not always produce the same effect and toxic symptoms have developed after a dosage ranging from 86 to 760 g. This suggests the existence of individual hypersensitivity.

[The reconstruction of the lacrimal pathway in the common canaliculus surgery]. / La reconstruction de la loge lacrymale dans la chirurgie du canal d'union.

We describe a new technique for restoring lacrimal pathway anatomy in common canaliculus surgery. Fourteen patients (4 men and 10 women), with a mean age of 59 +/- 19 years, suffering from chronic epiphora caused by common canaliculus stenosis were operated on (18 procedures: 14 unilateral, 4 bilateral). We used a modified Dupuy-Dutemps technique. The anterior face of the lacrimal sac was cut as a flap, which was secured with the posterior nasal mucosal flap for the posterior anastomosis plane. The common canaliculus stenosis and the external face of the lacrimal sac were excised guided by the operating microscope so as to put in place a bicanalicular device, which was left for 6 months. The anterior plane of anastomosis was made of a Goretex((R)) patch or PTFE((R)) (Polytetrafluoroethylene((R))) placed under the deep face of the orbicularis muscle. The procedure was successful in 15 of the 18 cases (success rate: 83.3%). Among the three failures, two were due to the early loss of the bicanalicular stent and one to anastomosis fibrosis. This technique made it possible to restore lacrimal pathway anatomy, which was severely modified by the dacryocystorhinostomy procedure and to protect the anastomosis from fibrosis by the surrounding tissues. Biomaterials such as Goretex((R)) and PTFE((R)) are valuable tools for this technique. In common canaliculus stenosis, restoring the lacrimal pathway with biomaterials such as Goretex((R)) or PTFE((R)) improves the functional results.

[Intracorneal suture. A simple procedure for the correction of astigmatism after cataract operation]. / La suture intracornéenne. Un procédé simple de cure d'astigmatisme après intervention de cataracte.

A simple surgical procedure to cure post cataract-surgery astigmatism is reported. Corneo-corneal (sometimes corneo-scleral), 9-0 polyamide monofilament sutures are put in radially at the end (or at the two ends) of the flattest meridian to increase its curvature and therefore its refractive power. 14 eyes were treated by this procedure, 11 of them for an "against the rule" astigmatism (1st group) and the 3 others for a "with the rule" astigmatism (2nd group). No corneal incision or resection is performed before suturing. Surgery has been efficient in all cases. As compared to a mean pre-op against the rule astigmatism of 6.55 +/- 2.20 diopters, the post-op residual astigmatism was no more than 3.16 +/- 1.94, 2.66 +/- 1.17, 2.69 +/- 1.33 and 2.80 +/- 1.74 diopters, respectively 8 days, 3 months, 6 months, 12 months after the surgery. The average axis of the effect of the surgery was almost perpendicular to the initial axis of the astigmatism. The visual acuity also improved but was dependent on other factors in addition to the refractive surgery. The results were stable from 3 months after surgery and remained unchanged in those cases where the follow-up period was 18 months or more. No significative complications have been observed and side effects have been negligible. In our opinion, the results that we have obtained open the way to the intracorneal suture, without any section of the cornea, as a potential treatment for excessive astigmatism.

[Modifications in blood zinc and lead concentrations and ALA-dehydratase activity in optic neuropathy from alcohol and tobacco abuse]. / Modifications des concentrations sanguines du zinc, du plomb et de l'activité de l'ALA-dehydratase au cours des neuropathies optiques alcoolo-tabagiques.

Plasma red blood cell and total blood zinc levels were significantly decreased in 52 consecutives cases of bilateral, retrobulbar, axial optic neuropathy caused by chronic abuse of ordinary wine and/or beer and/or hard beverages and cigarette smoking principally in men in their forties [plasma zinc: 746 mg/l +/- 179 (n = 52), control 907 mg/l +/- 127; red blood cell zinc: 10,218 mg/l +/- 1,327 (n = 10), control 12,244 mg/l +/- 1,307; total blood zinc: 4,849 mg/l +/- 1,069 (n = 51), control 5,831 mg/l +/- 644]. In contrast, blood lead levels were increased in these cases - blood lead: 344 mg/l +/- 101 (n = 30), control 193 mg/l +/- 94. Activity of red blood cell delta-amino-levulinic acid dehydratase (ALA-dehydratase), a zinc dependent enzyme, was decreased [red blood cell ALA-dehydratase; 18,8 IU/l +/- 2,2 (n = 13), control 44,8 IU/l +/- 3,3]. Plasma magnesium was slightly decreased while serum copper was not significantly modified. Possible ophthalmological implication of these findings are discussed.

[Therapeutic affect of zinc sulfate on central scotoma due to optic neuropathy of alcohol and tobacco abuse]. / Effet thérapeutique du sulfate de zinc sur le scotome central des neuropathies optiques alcoolo-tabagiques.

The oral administration of 400 mg/day for one month of zinc sulphate, when compared with placebo, provoked normal plasma zinc level in treated patients, principally men in their forties, with bilateral, retrobulbar, axial, optic neuropathy related to excessive smoking and consumption of ordinary wine and/or beer and/or spirits. Treatment significantly improved visual capacity (measured with Friedmann analyser) of the central scotoma area (5 degrees).

[Scintigraphy of the lacrimal ducts: the value of the lateral view in the postoperative period]. / Scintigraphie des voies lacrymales: intérêt de l'incidence latérale en postopératoire.

Lacrimal scintillography, a simple, non traumatic, and physiological method, has been for a long time an useful exploration in the study of lacrimal excretory pathology. It allows an accurate diagnosis especially in the case of functional stenosis and, due to its ability to indicate the exact seat of obstruction, this technique is able to determine the surgical treatment required. This study underlines the contribution of lacrimal scintillography in the control of surgical anastomosis permeability, because of a modification in the initial technique: the use of scintillography in employing the lateral view rather than the front view, usually used, permits a better visualisation of the new surgically created excretory passage, particularly in the posterior area of nasal fossae.

[Scintigraphy of the lacrimal ducts. Value of the lateral incidence in postoperative period]. / Scintigraphie des voies lacrymales. Intérêt de l'incidence latérale en postopératoire.

Lacrimal scintillography, a simple, non traumatic, and physiological method, has been for a long time an useful exploration in the study excretory pathology. It allows an accurate diagnosis especially in the case of functional stenosis and, due to its ability to indicate the exact seat of obstruction, this technique is able to determine the surgical treatment required. This study underlines the contribution of lacrimal scintillography in the control of surgical anastomosis permeability, because of a modification in the initial technique: the use of scintillography in employing the lateral view rather than the front view, usually used, permits a better visualisation of the new surgically created excretory passage, particularly in the posterior area of nasal fossae.

[Gonioretraction using argon laser]. / La goniorétraction au laser à argon.

Argon laser trabeculoplasty (ALT) has recently become one of the most popular procedures in the treatment of chronic open angle glaucoma. Although ALT is quite efficient, its mode of action is far from understood and the rate of complications or side effects is not negligible. In 1981 we began exploring a different procedure that we have called argon laser gonioretraction (ALG) with reference to the Cairns surgical goniospasis. While the corneo-scleral trabeculum is the target for argon laser beams in ALT, in ALG the beams are directed toward the ciliary band in an attempt to get the scar to pull the scleral spur backwards and stretch the trabeculum. The procedure may also act through the uveal trabeculum. The procedure was first utilized from 1981 to 1983 in 43 chronic open angle glaucoma eyes with: 1/ a high rate of success in decreasing the intraocular pressure on a long term basis, 2/ an acceptable rate of complications. 18 months after laser surgery, intraocular pressure was fully controlled without any medical treatment in 19 cases (44%). 18 additional cases (42%) were controlled with the help of less medical treatment than before. In 4 cases (8%) the failure was complete including one case with significant prolonged and non-responsive post-op hypertension which has induced a slight alteration of the visual field. One case was lost to follow-up. Supposed advantages of ALG over ALT are: integrity of the corneo-scleral trabeculum is maintained, goniosynechiae are more peripheral, and there is less propensity to induce proliferation of endothelial cells.

[Chronic alcohol-tobacco poisoning: towards an early detection of optic neuropathy]. / Intoxication alcoolo-tabagique chronique: vers un dépistage précoce de la neuropathie optique.

Forty-two patients (33 men, 9 women) with normal visual acuity admitted to an alcoholism rehabilitation programme were evaluated for colour vision using the automatized Fransworth-Munsell test (ChromopsR) and for central visual field using Friedmann's analyser. An early colour blindness without axis, i.e. a lack of colour discrimination, was often found. At the same time, in the more intoxications perimetric defects appeared in the 30 degrees area first centrally, then followed by arcuate superior scotomas.

[Myopia in pseudoxanthoma elasticum]. / Le pseudoxanthome élastique et la myopie.

INTRODUCTION: Refraction in patients with pseudoxanthoma elasticum (PXE) has not yet been studied in the literature. The purpose of our study was to determine if PXE may be associated with myopia, similarly to Marfan syndrome, another collagen-vascular disease. PATIENTS AND METHODS: This cross-sectional study evaluated 53 consecutive patients (32 women and 21 men, mean age 50 ± 16) from September 2009 to June 2011, with 53 age- and sex-matched controls. For each patient, we measured spherical equivalent, visual acuity, keratometry, axial length and crystalline lens power of each eye. Results were compared with Student's t-test. RESULTS: There was a significant difference between the mean values of myopia in the PXE population (-0.98) compared to the group of healthy controls (-0.33, P<0.0093). There was no significant difference between the two groups for the axial length (23.9 mm versus 23.69 mm; P=0.236), keratometry (43.53 versus 43.44; P=0.68), lens power (22.03 versus 21.71; P=0.225). DISCUSSION: PXE induces calcification of elastic fibers in various human tissues (skin, retina, vascular walls). Since there are no elastic fibers in the cornea or lens, we assume that the elastic zonular fibers may be pathologic in PXE patients. This could result in an anterior displacement of the lens in PXE, which could explain the moderate myopia. CONCLUSION: PXE may be associated with mild myopia compared to healthy controls. Additional studies, including more patients and evaluating anterior chamber depth and zonular histology are necessary to confirm these preliminary findings.

[Systemic conditions associated with central and branch retinal artery occlusions]. / Apports du bilan étiologique des occlusions de l'artère centrale de la rétine et de ses branches et conséquences thérapeutiques.

INTRODUCTION: Retinal artery occlusions (RAO) are severe conditions threatening vision, affecting the subsequent mortality of these patients. PATIENTS AND METHODS: We retrospectively reviewed the work-up performed in all patients diagnosed with retinal artery occlusions evaluated in two university hospitals in France (Tours and Angers). RESULTS: A total of 131 patients (131 eyes) with RAO were included, with a mean age of 69.5years and male predominance (64 %). Central retinal artery occlusion (CRAO) resulted in poor initial visual acuity (90 % less than count fingers), whereas those with branch retinal artery occlusion (BRAO) had better visual acuity (63.6 % better than 20/40). Systemic arterial hypertension (HTN) was the most common associated risk factor. Carotid stenosis was found in 50 % of cases, leading to endarterectomy in nine patients (6.9 %), while an underlying cardiac cause was implicated in 14 % of cases. Giant cell arteritis was diagnosed in five patients (3.8 %). DISCUSSION: Work-up of RAO may detect treatable cardiovascular and systemic conditions, allowing prevention of further ocular recurrence or stroke. CONCLUSION: Etiologic work-up of retinal arterial occlusion can diagnose potentially treatable underlying systemic conditions, such as giant cell arteritis, cardiac conditions and extracranial cerebrovascular disease. Giant cell arteritis has to be ruled out at the acute phase, while the role and timing of semi-urgent testing (supra-aortic Doppler echography, echocardiography, electrocardiography, lab work-up) or delayed testing (transesophageal echocardiography, brain imaging) have yet to be determined.