Conjunctival involvement in familial amyloidotic polyneuropathy

The present study is an evaluation of the possibility of using conjunctival biopsies for establishing the diagnosis of systemic amyloidosis of neuropathic type. Amyloid deposits were demonstrated in conjunctival biopsies from 15 of 16 patients with polyneuropathy and from 1 of 4 patients with vitreous opacities as the only symptom. Thus the sensitivity of conjunctival biopsies for the diagnosis of systemic amyloidosis of this type is similar to that of biopsies from other tissues. It is concluded that a conjunctival biopsy is a useful diagnostic tool since the technique is simple and there is little discomfort for the patient.     

Bilateral corneal perforation in familial amyloidotic polyneuropathy

Purpose We report the progression of bilateral central perforating ulceration in the cornea of a patient with familial amyloidotic polyneuropathy (FAP), also known as hereditary Portuguese amyloidosis, who received two corneal grafts in an interval of 6 years. The pathology of the original host and the grafted cornea is described.Methods Overall histology and immunolocalization of transthyretin, amyloid beta (A), and epithelial and inflammatory markers were performed.Results Corneal sensitivity and tear film were reduced. The grafted but not the original tissue contained amyloid deposits with transthyretin immunoreactivity. Epithelial and stromal thinning was accentuated in the graft, with epithelial dysplasia, hyperproliferation, and parakeratosis. Abundance of basement membrane material in hyperproliferative regions suggested recurrent attempts of wound healing. Activated keratocytes, ingrowth of vessels, infiltrated inflammatory, and immune cells reflect both acute and chronic inflammation.Conclusion Amyloid deposits may progressively reduce corneal sensitivity and damage epithelium and stroma. Corneal neuropathy, together with impaired tear film, may entail the pathology of dry eyes as a bystander effect, contributing to exacerbation of epithelial injury, deregulated proliferation, and parakeratosis. Once established, both acute and chronic inflammation may sustain progression of the corneal pathology.     

Ocular microangiopathy in familial amyloidotic polyneuropathy,type I

To obtain precise information on ophthalmological manifestations in patients with familial amyloidotic polyneuropathy (FAP), we performed ophthalmological and histopathological studies on 18 FAP patients and 6 asymptomatic individuals with a mutant transthyretin (TTR) gene. The incidence of vascular abnormalities of the conjunctiva and retina was surprisingly high in FAP patients. Abnormal conjunctival vessels were found mainly in the limbal area of FAP patients, but not in asymptomatic individuals with a mutant TTR gene. Conjunctival biopsy of 5 FAP patients and autopsy of another 2 FAP patients revealed that a significant amyloid deposit could be recognized in the superficial substantia propria of the conjunctiva and wall and perivascular area of the conjunctival vessels in all cases, a finding that is of diagnostic value. As for the retinal vessels, an abnormal arteriovenous ratio (A/V ratio), tortuous retinal vessels, cotton wool exudates and retinal hemorrhages were found in FAP patients. However, histopathological analysis of the retina in two autopsied cases revealed only a trace amount of amyloid deposit aruund the retinal vessels. Ophthalmological examination of three patients with pandysautonomia revealed that the appearance of both the conjunctival and retinal vessels of these patients was similar to that in FAP patients. These results indicate that in FAP patients ocular microangiopathy may be related to autonomic dysfunction as well as amyloid deposit. Offprint requests to: E. Ando     

Aqueous outflow system in familial amyloidotic polyneuropathy,Portuguese type

Familial amyloidotic polyneuropathy (FAP) is a hereditary disease which may present a wide range of ocular manifestations. Glaucoma is amongst the most serious complications of FAP. We report the results of ultrastructural study of the trabecular meshwork in a glaucomatous patient with the Portuguese form of FAP. This study showed that there was marked anatomical disruption of the uveoscleral, corneoscleral meshworks and juxtacanalicular tissue characterized by (a) accumulation of amyloid fibrils in the intertrabecular spaces; (b) degeneration of the endothelial cells; (c) homogeneous and/or multilayered plaques of basement membrane-like material loading the intertrabecular spaces or protruding to the lumen of the Schlemm's canal; and (d) degeneration of unmyelinated nerve fibres. These morphological changes and an analysis of the literature suggest that mechanical and neuropathic events can be co-existing factors which enhance the resistance to aqueous humour outflow, leading to increased intraocular pressure and glaucoma in the Portuguese form of FAP.     

Vitreous opacities and outcome of vitreous surgery in patients with familial amyloidotic polyneuropathy

PURPOSE: To report the prevalence of vitreous opacities and the outcome of vitreous surgery in patients with familial amyloidotic polyneuropathy (FAP). DESIGN: Observational case series. METHODS: In 37 patients with FAP and the ATTR Val30 Met mutation, vitreous opacities were present in 14 eyes of 9 patients and vitrectomy combined with phacoemulsification and intraocular lens implantation was performed in five eyes of three patients. In six patients with the ATTR Tyr114Cys mutation, vitreous opacities were present in both eyes of all six patients and vitrectomy combined with phacoemulsification and intraocular lens implantation was performed in nine eyes of six patients. The mean follow-up period after vitreous surgery was 20.9 +/- 16.8 months (range, 3 to 52 months). RESULTS: The prevalence of vitreous opacities is much higher in patients with ATTR Tyr114Cys (100%) than in those with ATTR Val30 Met (24%). The mean age at the onset of vitreous opacities was significantly lower in the patients with ATTR Tyr114Cys (37.0 +/- 5.3 years) than in the nine patients with ATTR Val30 Met (52.8 +/- 9.1 years; P <.005). Visual acuity improved in all 14 eyes after vitreous surgery; however, final visual acuity decreased in one eye owing to the occurrence of a central retinal vein occlusion. Vitreous opacities mildly increased in two eyes. CONCLUSIONS: Our data suggest that the ATTR Val30 Met and ATTR Tyr114Cys mutations induce different clinical features of vitreous opacities. Vitreous surgery combined with phacoemulsification and implantation of an intraocular lens is a safe and useful treatment. Careful long-term follow-up should be performed.     

Ocular manifestations of familial amyloidotic polyneuropathy type I: long term follow up

AIMS—To obtain precise information on ocular manifestations of familial amyloidotic polyneuropathy (FAP) type I, the incidence of five main ocular manifestations—abnormal conjunctival vessels (ACV), keratoconjunctivitis sicca (KCS), pupillary abnormality, vitreous opacity, and glaucoma, were compared through long term follow up.
METHODS—Ocular examinations were performed in 37 FAP type I patients (Met30) from once to 12 times over a period of 1 to 12 years and 7 months.
RESULTS—The following incidences were observed on initial examination of each patient with FAP: ACV in 75.5%, pupillary abnormalities in 43.2%, KCS in 40.5%, glaucoma in 5.4%, and vitreous opacity in 5.4%. All ocular manifestations increased with the progression of FAP, and the incidence of ACV reached 100% during follow up: this may be helpful in the diagnosis of FAP.
CONCLUSION—Since no precise statistical ocular study on FAP with long term follow up has been performed, this report may provide important information to help elucidate the mechanism of the amyloid distributing process in the amyloid targeted organs of FAP and to provide the natural course of ocular manifestations of FAP.

     

Zinn-Haller arterial ring observed by ICG angiography in high myopia

AIMS—To delineate the entire Zinn-Haller arterial ring angiographically in vivo.
METHODS—382 highly myopic eyes (210 patients) with refractive errors greater than −8.25 D were examined using indocyanine green (ICG) videoangiography. A control group of 80 eyes (40 patients) had refractive errors within plano +/− 3 D.
RESULTS—The Zinn-Haller ring was visible in 206 of 382 highly myopic eyes (53.9%) by ICG angiography. Although only a part of the Zinn-Haller ring was visible in 162 of 206 eyes, in the remaining 44 eyes it was observed almost completely around the optic nerve head. No anastomotic channels between lateral and medial short posterior ciliary arteries were filled by ICG angiography. In 22 of the 44 eyes (50.0%) the Zinn-Haller ring was supplied by branches of the lateral and medial short posterior ciliary arteries; in seven eyes, it was supplied only by the lateral short posterior ciliary artery; and in seven eyes, it was supplied only by the medial short posterior ciliary artery. In none of the control subjects was the Zinn-Haller ring visible by ICG angiography.
CONCLUSIONS—The Zinn-Haller ring observed by ICG angiography was not a complete collateral circle between lateral and medial posterior ciliary arteries. Also, the patterns in supply vessels to the Zinn-Haller ring varied. ICG angiography made possible the detailed observation of the Zinn-Haller ring in human eyes in vivo.

Keywords: Zinn-Haller circle; blood flow; optic nerve head; myopia     

Early onset vitreous amyloidosis in familial amyloidotic polyneuropathy with a transthyretin Glu54Gly mutation is associated with elevated vitreous VEGF

Aim

To report the early vitreous involvement in a rare familial amyloidotic polyneuropathy (FAP) mutation and associated vitreous vascular endothelial growth factor (VEGF) levels.

Design

Observational case series.

Methods

Review of clinical, pathological, photographic,and angiographic records of two FAP siblings with severe vitreous involvement. Laboratory ELISA analysis of vitreous samples for VEGF, and DNA sequence analysis of peripheral blood for transthyretin (TTR) mutational analysis.

Results

Two patients underwent 25‐gauge vitrectomy in three eyes with marked improvement of visual acuity. Neovascularisation seen intraoperatively responded to endolaser. Analysis of vitrectomy samples for VEGF showed raised levels in all three specimens. Mutational analysis revealed an isolated Glu54Gly mutation in the transthyretin gene.

Conclusions

Early involvement of the vitreous occurs in a rare transthyretin mutation of FAP, with increased vitreous levels of VEGF.     

Precise monitoring and differentiation of inflammatory events by indocyanine green (ICG) angiography in a case of recurrent posterior sarcoid uveitis

PURPOSE: By providing information on choroidal lesions, indocyanine green (ICG) angiography is complementary to fluorescein angiography in the workup of posterior uveitis. The aim here was to illustrate practically the suitability of performing dual fluorescein/ICG angiograms in a demonstrative case of recurrent presumed posterior sarcoid uveitis. METHODS: Sequential dual fluorescein/ICG angiograms were performed for the workup and follow-up of a case of recurrent presumed sarcoid uveitis. RESULTS: Dual fluorescein and ICG angiograms performed during the first recrudescence of inflammation showed mainly retinal involvement with cystoid macular edema, diffuse posterior pole retinal hyperfluorescence, and papillitis, whereas the second recurrence after tapering oral corticosteroid therapy showed new choroidal lesions of the posterior pole in the absence of significant retinal involvement. CONCLUSIONS: Dual fluorescein/ICG angiography clearly allowed the differentiation of two different inflammatory events, one involving the retina and the other involving the choroid, at the origin of similar clinical manifestations.     

Magnetic resonance angiography of vascular lesions causing neuro-ophthalmic deficits

Magnetic resonance angiography (MRA) is a noninvasive, rapidly evolving technique for imaging the intra- and extracranial carotid and vertebrobasilar circulations. It may in some circumstances obviate conventional angiography and the accompanying risks associated with catheterization and contrast injection. MRA exploits the different physical properties between moving protons and stationary tissue to yield flow sensitive data in the form of anatomic images or velocity and flow measurements. Since patients with various vascular disorders may present exclusively with ophthalmologic signs and symptoms, it is expected that MRA will become more frequently utilized by ophthalmologists. The exact role of MRA in the workup of vascular disorders remains to be more precisely defined, pending the performance of additional well-controlled standardized studies. At present, MRA is utilized to complement the conventional spin-echo studies of patients with arterial and venous occlusion, vascular malformations, intracranial aneurysms, and neoplastic vascular invasion. With further refinements, it is expected that MRA will become a standard diagnostic tool for the evaluation of patients with vascular disorders.     

Choroidal thickening in a case of carotid cavernous fistula

A 47-year-old woman was diagnosed with dural carotid cavernous fistula (CCF) in her right eye (RE). Scans of the choroid using Spectralis optic coherence tomography (OCT) demonstrated significant asymmetry in subfoveal choroidal thickness (RE 451 μm, left eye (LE) 367 μm). This asymmetry disappeared after the fistula was embolizated through the ophthalmic artery (RE 341 μm; LE 340 μm). This case suggests that OCT should be considered as an ancillary test in the diagnosis of CCF.