Amyloidosis and Ocular Involvement: an Overview

ABSTRACT

Purpose: To describe the ophthalmic manifestations of amyloidosis and the corresponding therapeutic measures.

Methods: The 178 patients included in the study had different types of amyloidosis, diagnosed at a single internal medicine institution (Bari, Italy). To provide a comprehensive review of the types of amyloidosis that can be associated with ocular involvement, the images and clinical descriptions of patients with amyloidosis structurally related to gelsolin, keratoepithelin and lactoferrin were obtained in collaborations with the ophthalmology departments of hospitals in Mainz (Germany) and Helsinki (Finland).

Results: Overall, ocular morbidity was detected in 41 of the 178 patients with amyloidosis (23%). AL amyloidosis was diagnosed in 18 patients with systemic disease, 3 with multiple myeloma, and 11 with localized amyloidosis. AA amyloidosis was detected in 2 patients with rheumatoid arthritis and 3 with Behçet syndrome, and transthyretin amyloidosis in 4 patients. The treatment of AL amyloidosis is based on chemotherapy to suppress the production of amyloidogenic L-chains and on surgical excision of orbital or conjunctival masses. AA amyloidosis is managed by targeting the underlying condition. Vitreous opacities and additional findings of ocular involvement in patients with transthyretin amyloidosis indicate the need for pars plana vitrectomy. Gelsolin amyloidosis, characterized by lattice corneal amyloidosis and polyneuropathy, results in recurrent keratitis and corneal scarring, such that keratoplasty is inevitable. In patients with lattice corneal dystrophies associated with amyloid deposits of keratoepithelin fragments, corneal transparency is compromised by deposits of congophilic material in the subepithelial layer and deep corneal stroma. Patients with established corneal opacities are treated by corneal transplantation, but the prognosis is poor because recurrent corneal deposits are possible after surgery. In patients with gelatinous drop-like dystrophy, the amyloid fibrils that accumulate beneath the corneal epithelium consist of lactoferrin and can severely impair visual acuity. Keratoplasty and its variants are performed for visual rehabilitation.

Conclusion: A routine ophthalmic follow-up is recommended for all patients with established or suspected amyloidosis, independent of the biochemical type of the amyloid. Close collaboration between the ophthalmologist and the internist will facilitate a more precise diagnosis of ocular involvement in amyloidosis and allow the multidisciplinary management of these patients.

Abbreviations: CD: corneal dystrophy; CLA: corneal lattice amyloidosis; CNS: central nervous system; CT: computed tomography; FAP: familial amyloidotic polyneuropathy; GDLCD: gelatinous drop-like corneal dystrophy; GLN: gelsolin; LCD: lattice corneal dystrophy; MRI: magnetic resonance imaging; OLT: orthotopic liver transplantation; TEM: transmission electron microscopy; TGFBI: transforming growth factor β induced; TTR: transthyretin.

Keywords:

• Amyloidosis
• gelsolin
• keratoepithelin
• lactoferrin
• transthyretin

Acknowledgments

This work was supported by APQ Ricerca Regione Puglia “Programma regionale a sostegno della specializzazione intelligente e della sostenibilità sociale ed ambientale - FutureInResearch”. The sponsor is a public organization that supports science in general, but it had no role in gathering, analyzing, or interpreting the data.

Conflict of interests

The authors report no conflict of interest.

Author contributions

RD and FD conceived and designed the study, and wrote the manuscript. GM and AV contributed to the study design and data interpretation. EG helped in the retrieval and collection of the data. WL and TK provided both information on the clinical features and the corresponding images of patients with relevant corneal dystrophies and corneal lattice amyloidosis. GM, WL and TK revised the manuscript for important intellectual content. All authors approved the draft submission, and accept responsibility for all aspects of this study.

Additional information

Funding

This work was supported by APQ Ricerca Regione Puglia “Programma regionale a sostegno della specializzazione intelligente e della sostenibilità sociale ed ambientale - FutureInResearch”. [None].