Int Ophthalmol (2016) 36:281–298
DOI 10.1007/s10792-015-0138-7
REVIEW
Ocular adnexal and orbital amyloidosis: a case series
and literature review
Eduardo R. Mora-Horna . Rubı́ Rojas-Padilla . Vianhi G. López .
Martı́n J. Guzmán . Ariel Ceriotto . Guillermo Salcedo
Received: 8 April 2015 / Accepted: 7 October 2015 / Published online: 14 October 2015
Ó Springer Science+Business Media Dordrecht 2015
Abstract The purpose of the study was to describe
the main clinical and epidemiologic characteristics,
treatment options, and outcome in a large series of
patients with periocular and orbital amyloidosis. This
is a retrospective, descriptive, observational study of a
case series of 14 patients with periocular and orbital
amyloidosis and is a review of previously published
cases with this diagnosis between September 2004 and
January 2015. In this study, we analyzed our 14
patients in conjunction with 69 well-documented
cases of orbital and/or periocular amyloidosis previ-
ously reported, with a total of 83. Of these, 54 were
female (65.1 %), 28 male (33.7 %), and one with
unspecified gender. The mean age at diagnosis was
54.9 years (range, 18–87). The localization of the
amyloidosis was classified as superficial, deep and
combined, with involvement of 53 (63.9 %), 26
(31.3 %), and four cases (4.8 %) in each group,
respectively. The main findings in superficial amyloi-
dosis were mass or tissue infiltration (84.9 %) and
E. R. Mora-Horna (&)
V. G. López

M. J. Guzmán
A. Ceriotto
G. Salcedo
Orbital and Oculoplastic Service, Asociación para Evitar
la Ceguera en México I.A.P. ‘‘Dr. Luis Sánchez Bulnes’’,
Vicente Garcı́a Torres 46, Delegación Coyoacán, Barrio
San Lucas, 04030 Mexico City, D.F., Mexico
e-mail: emorahorna@hotmail.com
R. Rojas-Padilla
Department of Dermatology, Hospital Infantil de México
Federico Gómez, Mexico City, D.F., Mexico
ptosis (30.2 %) and, in the cases with deep involve-
ment, mass (65.4 %), proptosis (57.7 %), limited
ocular movements (34.6 %), ocular displacement
(30.8 %), and ptosis (26.9 %). The cases with com-
bined involvement presented with signs and symptoms
of the two groups. Regarding the outcome, 43 patients
were reported stable after the diagnosis and 21 had
recurrence or required new surgical procedures. Peri-
ocular and orbital amyloidosis is a rare disease that can
present with a variety of symptoms and signs
depending on the localization and extension of
involvement. Its prompt recognition is important in
order to investigate systemic disease, which will affect
the prognosis of each case.
Keywords Amyloidosis
Orbital
Adnexal

Lacrimal
Conjunctival
Introduction
Amyloidosis is a disorder of diverse etiology charac-
terized by deposits of abnormally folded proteins,
mainly in the extracellular spaces of organs and tissues
[1]. Rudolph Virchow, in 1854, introduced and
popularized the term amyloid to denote a macroscopic
tissue abnormality that exhibited a positive iodine
staining reaction [2].
The deposited amyloid material is distinguished by
the following characteristics: rigid, non-branching
fibrils that bind the dye Congo red and exhibit green,
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yellow or orange birefringence when the stained
deposits are viewed by polarization microscopy;
amorphous eosinophilic appearance on hematoxylin
and eosin staining; and a cross-b diffraction pattern
when analyzed by X-ray diffraction [1, 3]. To date,
there are 31 known extracellular fibril proteins in
humans, two of which are iatrogenic (subcutaneous
insulin and enfuvirtide) [3, 4]. The chemical identity
of these fibril proteins is the base of the amyloid fibril
nomenclature; clinical classification of the amyloido-
sis should be as well [3].
According to the extent of involvement, amyloido-
sis can be classified as local, when the amyloid is
restricted to a particular organ or tissue [5–7], or
systemic, if amyloid is present in two different sites of
the body or if amyloid has been detected in only 1 site
of the body in combination with a classic picture of
amyloidosis at an alternate site [8].
The occurrence of amyloid in the eye and in the
ocular adnexal structures is well known but uncom-
mon; it can be found as part of a systemic amyloidosis
or as a localized phenomenon [9]. Sites of periocular
and orbital amyloid deposit are the lacrimal gland and
sac, eyelid, conjunctiva, ocular adnexa, extraocular
muscles, and levator palpebrae muscle [10–12].
The most common clinical signs are visible or
palpable periocular mass or tissue infiltration, ptosis,
periocular discomfort, proptosis, globe displacement,
limitation in ocular motility and recurrent subcon-
junctival hemorrhages [13].
In this review, we describe the main clinical
characteristics in a series of 14 patients with orbital
and/or periocular amyloidosis diagnosed between
1994 and 2014.
Materials and methods
We reviewed the medical files of all patients with
orbital and/or periocular amyloidosis confirmed by
histopathological study at Asociación para Evitar la
Ceguera en México I.A.P. ‘‘Dr. Luis Sánchez Bulnes’’
between January 1994 and October 2014, finding 14
patients and describing their main clinical character-
istics. The study adhered to the principles outlined in
the Declaration of Helsinki and was approved by the
Ethical Review Board of the hospital.
We also searched all the articles in English using
PUBMED with the combination of keywords
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conjunctival amyloidosis, orbital amyloidosis, lacri-
mal and amyloidosis, eyelid and amyloidosis between
September 2004 and January 2015; some of the
references cited in those articles were additionally
reviewed. We only included well-documented case
series and individual case reports. Finally, we ana-
lyzed our patients with the rest of the cases that
fulfilled the previous criterion.
Case reports
Case 1
An 18-year-old female patient complained of an
8-month history of recurrent hyposphagma of left
eye (OS). Visual acuity was 20/20 in both eyes (OU).
Right eye (OD) appeared normal. Deposits of friable,
yellowish material among engorged vasculature were
noted in the bulbar conjunctiva of OS (Fig. 1a).
Conjunctival amyloidosis was suspected and inci-
sional biopsy of the lesion was performed. Amor-
phous, eosinophilic, Congo red positive deposits were
demonstrated on the histopathological analysis. Fur-
ther studies ruled out systemic amyloidosis. Patient
remains without hyposphagma on 5-month follow-up.
Case 2
A 41-year-old female patient reported a 6-year history
of conjunctival amyloidosis in OS associated with
ptosis and eyelid swelling. Visual acuity was 20/20
and 20/40 in OD and OS, respectively. A diffuse,
papilliform and pink-yellowish lesion was observed
on the superior tarsal conjunctiva of OU (Fig. 1b).
Recurrent amyloidosis was suspected. Biopsy of the
conjunctival lesion and levator aponeurosis reinsertion
was performed in OS. Amorphous, eosinophilic,
Congo red positive deposits were demonstrated on
the histopathological analysis. Systemic evaluation
revealed the absence of systemic amyloidosis. Patient
is stable upon 24-month follow-up.
Case 3
Fifty-nine-year-old male patient reported with an
unremarkable history for other pathologies. He pre-
sented with conjunctival lesions and intermittent
redness of OU, which he noted 3 months prior to
Int Ophthalmol (2016) 36:281–298
Fig. 1 a Case 1
hyposphagma and yellowish
material deposits in the
superior bulbar conjunctiva.
b Case 2 diffuse, papilliform
and pink-yellowish lesion
on the superior tarsal
conjunctiva. c Case 3
diffuse, yellowish and
salmon-like patch in the
inferior bulbar and tarsal
conjunctiva. d Case 4
salmon-like mass on inferior
fornix and temporal bulbar
conjunctiva
arrival to our hospital. Visual acuity was 20/20 in OU.
OD showed non-painful, diffuse, yellowish, salmon-
like patch in the inferior bulbar and tarsal conjunctiva,
with apparently no deep tissue attachment (Fig. 1c).
OS had similar findings plus another lesion in the
superotemporal quadrant of the bulbar conjunctiva.
Conjunctival lymphoma was suspected and incisional
biopsy of OU was performed. Histopathological
analysis revealed multiple, amorphous, eosinophilic,
Congo red positive deposits, with green birefringence
when observed under polarized light. Patient was
referred to a specialty clinic for systemic studies,
which have not been carried out; he remains
stable upon 20-month follow-up.
Case 4
An 84-year-old patient, with a history of hypertension
and open angle glaucoma, complained of diminished
visual acuity in OD and ocular surface symptoms.
Visual acuity was 20/80 in OD and no light perception
in OS since 6 years ago. In the superotemporal, fornix
and bulbar conjunctiva of OS, vascularized, salmon-
like patches were noted (Fig. 1d); posterior pole
presented papillary atrophy and age-related macular
degeneration. A lymphoproliferative disease was
suspected and conjunctival biopsy was performed.
283
Extracellular deposits of amorphous, eosinophilic,
Congo red positive material, among moderate plas-
matic cell infiltrates, were reported on the histopatho-
logical analysis. Systemic amyloidosis was ruled out;
she remains stable after 15-month follow-up.
Case 5
Sixty-three-year-old female presented with a 3-year
history of painful, upper eyelid swelling, decreased
visual acuity in OD, and double vision. Upon exam-
ination, visual acuity was 20/80 in OU. A firm, painful
lesion with no clear margins was palpable in the
superior orbital rim of the OD, which also showed
ptosis and swelling of superior and inferior eyelids.
Inferior ocular displacement and 3-mm proptosis, with
limitation to up gaze and down gaze, was noted
(Fig. 2a). Anterior chamber and posterior pole
appeared normal. OS was remarkable only for a
posterior subcapsular opacity of the lens, without other
findings. Computed tomography (CT) scan showed a
diffuse lesion in the right orbit roof which affected
lacrimal gland and superior and lateral rectus muscles,
with intralesional calcifications (Fig. 2b). A metastatic
lesion was suspected so orbital biopsy via superior
lateral sulcus was performed in OD. Macroscopic
appearance of the obtained tissue was yellowish and
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Fig. 2 Case 5 a ptosis, superior and inferior eyelid swelling,
inferior ocular displacement and proptosis. b CT scan showed a
diffuse lesion in the right orbit roof with involvement of lacrimal
gland, superior and lateral rectus muscles with intralesional
calcifications
friable. Our pathology department reported abundant,
amorphous Congo red positive deposits, with green
birefringence when observed under polarized light,
and bone metaplasia. Systemic studies were ordered.
Patient never returned to further follow-up visits.
Case 6
A 73-year-old female patient with a history of
rheumatoid arthritis (RA), trachoma and probable
rosacea complained of hyperemia, pruritus and tearing
of both eyes 20 years prior to this examination. Visual
acuity was 20/50 and 20/100 in OD and OS, respec-
tively. Bulbar conjunctiva in the OD appeared swollen
and hyperemic, with a thickened tarsal conjunctiva
with gigantic papillae and telangiectasia in the inferior
margin. OS was only remarkable for chemosis of the
inferior conjunctiva. Rosacea was suspected. A wedge
biopsy of the lesion was performed. Extracellular
deposits of amorphous, eosinophilic, Congo red
positive material were reported on the histopatholog-
ical analysis. Patient was referred for systemic eval-
uation, but missed follow-up visits.
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Case 7
A 69-year-old patient with RA referred a 6-year
history of recurrent hyposphagma in OD, associating
with foreign body sensation and pruritus. Visual acuity
was 20/20 in OU. OD showed diffuse, yellowish
subconjunctival deposits and hyposphagma. Conjunc-
tival amyloidosis was suspected and incisional biopsy
was performed in OD. Histopathological analysis
revealed multiple, amorphous, eosinophilic, Congo
red positive deposits, with green birefringence when
observed under polarized light. Systemic amyloidosis
was ruled out. Patient died 13 years after the biopsy
from unknown reasons.
Case 8
A 65-year-old male patient with type two diabetes and
hypertension presented with a corneal ulcer in OS;
randomly, a conjunctival lesion was noted in the same
eye. Visual acuity was 20/25 in OD and 20/50 in OS.
Anterior segment was normal in OD. A salmon-like
plaque with well-defined margins was described in the
inferior tarsal and bulbar conjunctiva of OS. Although
scar tissue secondary to chalazion was the probable
diagnosis, excisional biopsy was performed. Extra-
cellular deposits of amorphous, eosinophilic, Congo
red positive material were reported on the histopatho-
logical analysis. Patient did not return to follow-up.
Case 9
A 22-year-old female patient with amblyopia of OS
referred a 4-month history of tearing and superior and
inferior painful eyelid swelling in OS. Visual acuity
was 20/20 in OD and counting fingers in OS. OD was
normal. A palpable, non-painful, firm lesion was noted
in the superolateral orbital rim of OS. Also, an inferior
ocular displacement (5 mm) was described. An irreg-
ular, isodense lesion with intralesional calcifications
that infiltrated lacrimal gland, extending to the roof
and lateral orbital wall, was reported on CT scan.
Lacrimal gland adenocarcinoma was suspected and
excisional biopsy of the lesion via lateral orbitotomy
was performed. Lytic lesions in the orbit were
observed during surgery. Histopathological analysis
reported multiple, partially calcified, amorphous nod-
ules among lymphoplasmacytic inflammatory infil-
trates. The deposits showed Congo red positivity and
Int Ophthalmol (2016) 36:281–298
green birefringence. Nine years later, a nasopharyn-
geal lesion compatible with amyloidosis was discov-
ered, requiring multiple surgeries ever since due to
respiratory and orbital complaints. Systemic amyloi-
dosis has been ruled out.
Case 10
A 40-year-old female patient with hypertension and
migraine presented with a 4-year history of upper
eyelid swelling, itching, and foreign body sensation in
OS. Visual acuity was 20/20 in OU. OD was normal. A
soft, well-defined lesion was palpable below the
orbital rim. Ultrasonography reported a lesion
(6 mm 9 6 mm9 8 mm) of high reflectivity, involv-
ing the lacrimal gland. Dacryoadenitis was suspected,
and a biopsy was performed. Extracellular deposits of
amorphous, eosinophilic, Congo red positive material
were reported on the histopathological analysis.
Tissue exhibited green birefringence when observed
under polarized light. The patient complained of
frontal headache. Five years later, a frontal sinus
lesion was confirmed to be amyloidosis. Further
evaluation ruled out systemic amyloidosis. She is
stable at an 8-year follow-up.
Case 11
A 54-year-old patient presented with a 5-year history
of ptosis and swelling of the left upper eyelid. Visual
acuity was 20/20 in OU. Yellowish plaques were
observed in the upper tarsal conjunctiva of OD, with
similar findings in upper and lower tarsal conjunctiva
of OS. Differential diagnosis was a lymphoprolifera-
tive process versus conjunctival amyloidosis. Inci-
sional biopsy was performed in OU. Extracellular
deposits of amorphous, eosinophilic, Congo red
positive material, among moderate lymphoplasma-
cytic infiltrates, were reported on the histopathological
analysis. Systemic disease was ruled out. Patient
remains stable after 5-month follow-up.
Case 12
A 56-year-old patient with diabetes mellitus had a
history of painful swelling, tearing, and foreign body
sensation in OD. Anti-inflammatory medication was
prescribed without improvement of the symptoms, so
a palpebral tissue biopsy was performed in another
285
hospital, reporting unspecific inflammation. Searching
for a second opinion, the patient presented to our
hospital with visual acuity of 20/100 in OD and 20/20
in OS. A firm lesion, which was palpable below the
upper right orbital rim, affected the tarsal conjunctiva
and caused ptosis. The bulbar conjunctiva of the same
eye exhibited yellow infiltrating lesions throughout
the 360° of its surface. As amyloidosis was suspected,
an incisional biopsy of tarsal and bulbar conjunctiva
was performed. Extracellular deposits of amorphous,
eosinophilic, Congo red positive material were
reported on the histopathological analysis. Tissue
obtained exhibited green birefringence when observed
under polarized light. Ptosis of OD improved. Sys-
temic evaluation was ordered, but the patient missed
follow-up visits.
Case 13
An 87-year-old female patient with RA and diabetes
mellitus complained of a 7-month history of recurrent
hyposphagma and conjunctival hyperemia, associat-
ing with foreign body sensation and tearing of OS.
Visual acuity was 20/150 in OD and counting fingers
in OS due to non-proliferative diabetic retinopathy and
clinically significant macular edema in OU. Upon
examination, OD was normal and chemosis and
diffuse hyperemia, with a palpable lesion in the
temporal aspect of the left lower eyelid, were noted. A
lymphoproliferative process was suspected, and con-
junctival biopsy was performed. Extracellular deposits
of amorphous, eosinophilic, Congo red positive
material were reported on the histopathological anal-
ysis. Tissue exhibited green birefringence when
observed under polarized light. Patient was referred
to rule out systemic amyloidosis but missed follow-up
visits.
Case 14
A 59-year-old female patient complained of a 6-month
history of red eye and right lower eyelid swelling in
OD. Visual acuity was 20/40 in OD and 20/20 in OS. A
2 9 1 cm, non-painful, firm, mobile not attached to
deep tissue lesion with well-defined margins was
noted. OS was normal. Lymphoproliferative disease
was suspected and incisional biopsy was performed.
Extracellular deposits of amorphous, eosinophilic,
Congo red positive material were reported on the
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histopathological analysis. Tissue exhibited green
birefringence when observed under polarized light.
Systemic amyloidosis was ruled out. Six months later,
swelling of lower right eyelid recurred. A new
excisional biopsy was performed 3 years later. After
2-year follow-up, inferior entropion developed, caus-
ing corneal erosion and associated surface symptoms.
By then, the lesion was palpable under the whole
inferior right eyelid. Full-thickness excisional biopsy
was performed with reconstruction of lower eyelid
with Hughes technique. Patient is recurrence-free and
stable upon 6-year follow-up.
Results
In this study, we analyzed our 14 patients in conjunction
with 69 well-documented cases of orbital and/or
periocular amyloidosis previously reported, with a total
of 83 (Table 1). Of these, 54 were female (65.1 %), 28
male (33.7 %), and one with unspecified gender. The
mean age at diagnosis was 54.9 years (range, 18-87).
The mean duration of signs and symptoms was only
reported in 59 patients, being 32.4 months (range,
1 week–20 years). Sixty-three cases were unilateral
(75.9 %) and 20, bilateral (24.1 %). The localization of
the amyloidosis was classified as superficial (affecting
primarily eyelid and/or conjunctiva), deep (with
involvement of lacrimal gland, extraocular muscles
and/or retrobulbar tissues) and combined, with involve-
ment of 53 (63.9 %), 26 (31.3 %) and 4 cases (4.8 %),
in each group, respectively.
Thirty-three patients had ocular or systemic ante-
cedents, the most frequent being RA (n = 5), local
amyloidosis (n = 3), systemic amyloidosis (n = 3),
cardiac pathology (n = 3), nephropathy (n = 3),
history of cancer (n = 2), multiple myeloma (MM)
(n = 2), Sjögren syndrome (n = 2), and previous
ocular trauma (n = 2). Among other important
antecedents, we also found trachoma, concurrent
lipodermoid, pulmonary sarcoidosis, Graves’ disease
and discoid lupus erythematosus in single cases.
Of the cases with superficial involvement, 7
(13.2 %) were localized to the eyelid, 43 (81.1 %) to
the conjunctiva, and 3 (5.7 %) to both of them. The
bulbar conjunctiva was the only affected in 20 patients
(43.5 %), the palpebral in 15 (32.6 %) and both of
them in 9 (19.6 %), with unspecified conjunctival
localization in 2 cases. In this group, the chief
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complaints referred by the patients were ocular surface
symptoms (including redness, dry eye, foreign body
sensation, burn or sting) in 25 patients (47.2 %), eyelid
swelling/thickening in 14 (26.4 %) and subconjuncti-
val and subcutaneous periocular hemorrhages in 9
(17 %) and 2 (3.8 %), respectively. During the
examination, the main findings were a visible or
palpable mass or tissue infiltration in 45 cases
(84.9 %) and ptosis in 16 (30.2 %).
In the cases with deep involvement, the lacrimal
gland was affected in a total of 9 patients (34.6 %), in
2 of them compromising other orbital tissues. One or
more extraocular muscles were infiltrated in 5 cases
(19.2 %), with exclusive involvement in two of them,
and the lacrimal sac in 1 (3.8 %). The most common
presenting manifestations included a palpable or
image documented mass in 17 patients (65.4 %), with
intralesional calcification in nine of them, proptosis in
15 (57.7 %), limited ocular movements in 9 (34.6 %),
ocular displacement in eight (30.8 %), and ptosis in
seven (26.9 %).
Four cases (4.8 %) had involvement of both
superficial and deep tissues thus presenting with signs
and symptoms of the two groups.
In all the cases, the initial management was
surgical: incisional biopsy in 61 (73.5 %), excisional
biopsy in 17 (20.5 %), and surgical debulking in 5
(6 %).
In some cases, the histopathological study revealed
other local concurrent pathologies such as MALT
lymphoma (n = 3) and solitary osseous plasmacy-
toma (n = 1). An evaluation for systemic amyloidosis
was positive in 13 of the total 83 cases (15.7 %), some
of them associated to other conditions such as
Waldenström macroglobulinemia (n = 1) and mye-
loma (n = 4).
Regarding the outcome, 43 patients were reported
stable after the diagnosis, 21 had recurrence or
required new surgical procedures and 1 died suddenly
soon after the biopsy was made. In 18 cases, this
information is unavailable.
Discussion
In this study, we present the largest case series with
periocular and orbital amyloidosis of a single oph-
thalmologic center. We report the main characteristics
of 14 patients who were diagnosed at Asociación para
 Table 1 Summary of the main features of 83 patients with superficial, deep or combined amyloidosis
Author Age/sex Ocular or Eye Chief Clinical features/CT Localization Sys Treatment Histopathology Outcome
(year) systemic complaint/duration feature A
antecedents (months)

Landa 52/M Chronic Cardiac OU Recurrent subcutaneous Eyelid petechiae, and Conj Yes Bx Amyloidosis Patient died
(2004) failure, HT, hem of the eyelid and ecchymoses, no suddenly
[14] weight loss auricles/NA clinical signs in conj
Hamidi 27/F Ocular trauma OD Diplopia, proptosis/ LOM, proptosis, Medial and lateral No Muscle bx AL-amyloidosis New symptoms
(2004) 12 m exotropia, palpable rectus muscle (j) in OU,
[15] Lateral rectus muscle requiring new
Int Ophthalmol (2016) 36:281–298

sx
Dinakaran 60/F NA OD Ptosis, RSH, orbital Ptosis, prolapsing mass Right superior orbit NA Inc bx Amyloidosis Debulking 1 year
(2005) mass/12 m through the fornix later, then
[16] stable
61/F NA OS Ptosis/NA Ptosis, yellow and LG NA Inc bx Amyloidosis Stable
nodular mass in LG
Kaplan 44/NA Cervical OS Local swelling, visual Orbital mass Left orbit No Removal of AL-amyloidosis Stable
(2005) reactive disturbances/24 m mass (j)
[17] lymphoid
hyperplasia
Bernardini 57/M MM, ischemic OU ES, OSS/12 m Eyelid masses Upper and lower Yes Surgical Amyloidosis Eyelid, facial and
(2005) heart attack eyelids debulking oral rec
[18] requiring new
sx
Mun 62/F No OS ES/6 m Ptosis, ES, eyelid mass Upper eyelid No Exc bx Amyloidosis Rec and new exc
(2005) bx
[19]
Marcet 70/M No OS Epiphora, lacrimal sac Lacrimal sac mass with Lacrimal sac and No Bx AA and AL (k)- Stable
(2006) mass/36 m bone destruction lacrimal duct amyloidosis
[12]
Mahajan 65/F No OS Eyelid thickening/12 m Nodular mass in the Lower eyelid and No Inc bx AL-amyloidosis Stable
(2006) eyelid and conj conj (j)
[20]
Higgins 53/M Asthma, OU RSH, periorbital Subconj hem, periorbital Conj Yes Bx, AL-amyloidosis N/A
(2006) duodenal ulcer brusing, diplopia/NA ecchymosis, eyelid vincristine (j) and
[21] thickening, LOM and myeloma
adriamycin
Seider 63/F N/A OD Ptosis, OSS/2 m Ptosis, conj yellow mass Palpebral and No Inc bx and Amyloidosis Stable
(2006) bulbar conj, ptosis
[22] fornix, semilunar repair
fold
287

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 Table 1 continued
288

Author Age/sex Ocular or Eye Chief Clinical features/CT Localization Sys Treatment Histopathology Outcome
(year) systemic complaint/duration feature A

123
antecedents (months)

25/F N/A OS Conj mass/NA Conj mass Fornix No Inc bx Amyloidosis Sx of

entropion,
then stable
Cheng 65/F N/A OS ES/36 m Proptosis, LG LG No Exc bx AL-amyloidosis (k) Stable
(2006) enlarged/calcif
[23] 43/F No OU Eyelid fullness/9 m LG enlarged/calcif LG No Bx Amyloidosis Stable
Tyradellis 67/F Small tumor OS Eyelid mass/24 m Thickened eyelid, Lower eyelid, No Exc bx AL-amyloidosis Rec and
(2006) in the same ectropion, subconj yellow palpebral conj news exc
[24] location tumefaction bx
Demirci 45/M No OD Redness, conj mass/ Conj waxy yellow mass Caruncle No Exc bx AL-amyloidosis (k) Stable
(2006) 120 m
[25] 65/F Temporal OS Redness/1 m Yellow pink conj mass, Superior bulbar conj No Inc bx Amyloidosis Rec
arteritis subconj hem
86/F No OD Ptosis, conj mass/ Ptosis, yellow-pink conj Bulbar and palpebral No Inc bx Amyloidosis Rec
NA mass, subconj hem conj, anterior orbit
and upper eyelid
69/F No OU Conj mass/7 m Yellow-pink conj mass Inferior fornix No Inc bx AL-amyloidosis (k) Stable
42/F No OS RSH/48 m Ptosis, yellow pink conj Bulbar and palpebral No Inc bx Amyloidosis Stable
mass, subconj hem conj
56/M Primary OS RSH/2 m Yellow pink conj mass, Semilunar fold Yes Exc bx and Amyloidosis Stable
systemic subconj hem cryotherapy
amyloidosis
Gauba 30/F NA OD RSH with menstrual Conj mass Inferior fornix No Bx and Amyloidosis Rec
(2006) cycle/96 m debulking
[26]
Di Bari 64/F NA OS Ptosis, orbital mass, Ptosis, proptosis, oc dis, Extraconal mass, No Bx and Amyloidosis NA
(2006) proptosis, visual orbital mass, OHT, optic following de removal of
[27] acuity loss/3 m nerve head ischemia superior rectal mass
muscle
Oishi 62/M No OS Ptosis, ES and Ptosis, proptosis, eyelid Orbit Yes Bx, mass AL-amyloidosis Rec
(2006) pigmentation/48 m pigmentation/punctate reduction requiring
[28] calcif resectation new sx
of LM
Rawlings 40/F No OD Proptosis/6 m Palpable mass inside the Orbit, greater wing of No Bx Solitary osseous Rx then
(2007) orbital rim, proptosis sphenoid and middle plasmacytoma, stable
[29] cranial fossa AL-amyloidosis
(k)
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 Table 1 continued
Author Age/sex Ocular or Eye Chief Clinical features/CT Localization Sys Treatment Histopathology Outcome
(year) systemic complaint/duration feature A
antecedents (months)

Topalkara 72/F Sjögren syndrome, OD OSS, ptosis/NA Ptosis, salmon-colored conj Bulbar conj Yes Exc bx MALT Rx rec of
(2007) RA, discoid mass lymphoma, lymphoma
[30] lupus AL-
erythematosus, amyloidosis
HT, vertigo (j)
Hass (2007) 74/F No OS Blurred vision in Proptosis, cataracts/calcif Orbit intraconal No Bx and MALT NA
Int Ophthalmol (2016) 36:281–298

[31] OU/6 m space, removal of lymphoma,

mass AL-
amyloidosis
(k)
Paula 47/M No OS ES, painful mass, Proptosis, medial canthus Superior oblique Yes Bx Amyloidosis Bone
(2008) diplopia/NA mass, OHT/enlargement of muscle temporalis marrow
[32] superior oblique and and transplant,
medial rectus muscle superior rec
oblique
muscle
Bozkurt 40/F No OS Hyperemia, conj Yellow-pink conj mass Inferior bulbar conj No Inc bx Amyloidosis NA
(2008) mass/12 m
[33]
Khaira 69/M Familial renal OD ES/6 m Proptosis, oc dis, LOM, orbit Intra and No Bx and MALT Rx then
(2008) tubular defect, swelling, conj infiltration, extraconal orbit, debulking lymphoma, stable
[34] poor vision OD pale cupped optic disc conj and eyelid AL-
amyloidosis
59/F HT OS ES, diplopia/12 m Proptosis, oc dis, orbital Orbit with No Inc bx AL-amyloidosis Requiring
mass, LOM encasement of (j) with clonal new sx and
lateral rectus and infiltrate of Rx
inferior rectus plasma cells
muscle
Mesa- 57/F NA OS Conjunctiva lightly Conj semilunar fold mass Bulbar conj No Exc bx AA amyloidosis Stable
Gutiérrez colored plaque/
(2008) 12 m
[35]
Spitellie 39/F No OD Eyelid lump, ptosis/ Salmon-pink conj mass, Palpebral conj, No Inc bx Amyloidosis Stable
(2008) 36 m ptosis, oc dis anterior orbit
[36]
Menetti 27/F NA OD Proptosis/24 m Proptosis Orbit, Meckeĺs No Bx AL-amyloidosis Stable
(2009) cave, (k and j)
[37] infratemporal
fossa
289

123
 Table 1 continued
290

Author Age/sex Ocular or Eye Chief Clinical features/CT Localization Sys Treatment Histopathology Outcome
(year) systemic complaint/duration feature A

123
antecedents (months)

Prabhakaran 45/F NA OS ES, discomfort/3 m Ptosis, superior temporal LG No Inc bx Amyloidosis NA

(2009) [38] orbit mass, proptosis oc
dis, LOM
Maejima 61/F RA, chronic OU ES/NA ES Eyelid Yes Inc bx AA amyloidosis NA
(2009) [39] renal failure
Brown 46/F Pulmonary OU ES, OSS/NA LG enlargement LG Yes Inc bx AL-amyloidosis MM
(2010) [40] sarcoidosis (k and j), treatment,
MM then stable
Caggiati 30/M Local OU Ptosis, ES/NA Yellowish conj masses, Palpebral conj, fornix No Electro- Amyloidosis Stable
(2010) [41] amyloidosis ptosis and lacrimal cauterization
punctum and CO2 laser
Goshe 55/M MM OU Incidentally Bilateral masses on MRI OD: medial and Yes Bx Amyloidosis NA
(2010) [42] associated discovered orbital anterior orbit OS:
with masses on MRI superior orbit
amyloidosis
Khalifa 27/F PPD (?), OS OSS/24 m Yellow-pink infiltrated, Bulbar conj, corneal No Exc bx Amyloidosis Stable
(2010) [43] ocular midstromal lattice-like
trauma lines
Wu (2011) 72/M Grave disease OU Diplopia, dysphagia/ Diplopia, proptosis, LOM, Orbit and nasopharinx No Bx Amyloidosis Stable
[44] NA oc dis
Gonçalves 63/F No OU ES/24 m ES, palpable mass in both Anterior and deep No Bx Amyloidosis Stable
(2011) [45] orbit, LOM/calcif orbita,
Yerli (2011) 60/F NA OS Sweling in the eye/ Subconj hem, proptosis, Intraconal orbit No Bx Amyloidosis Stable
[46] NA LOM, orbital mass, oc
dis/calcif
Ray (2012) 41/M NA OS Nasal conjunctival Nodular nasal conj lesion Bulbar conj close to No Exc bx, Amyloidosis Stable
[47] growth/36 m limb cryotherapy
Abdallah 47/F NA OD ES, ptosis/144 m ES, ptosis, red-yellow Lower conj Yes Exc bx AL-amyloidosis NA
(2012) [48] mass (j)
Int Ophthalmol (2016) 36:281–298
 Table 1 continued
Author Age/sex Ocular or Eye Chief Clinical features/CT Localization Sys Treatment Histopathology Outcome
(year) systemic complaint/duration feature A
antecedents (months)

Al-Nuaimi 38/F No OU Recurrent corneal Ptosis, pink conj mass Palpebral conj No Bx and ptosis Amyloidosis Rec
(2012) [7] erosion/NA sx
86/M Unestable angina, OD Ephifora/NA Punctual eversion, orbital Superior and NA Bx Amyloidosis Stable
bilateral ptosis mass, proptosis, oc dis lateral orbital
mass
53/F Conj amyloidosis OS Conj mass, RSH/NA Conj mass, subconj hem Conj, fornix No Bx and Amyloidosis Rec
Int Ophthalmol (2016) 36:281–298

and medial curettage requiring

canthal mass new sx
68/M Sjögren syndrome, OU Ptosis, OSS/60 m Ptosis, conj mass Palpebral conj NA Bx and ptosis Amyloidosis Rec
Psoriasis sx requiring
new sx
81/F No OD ES/72 m Ptosis, ES Palpebral conj NA Bx, wedge Amyloidosis Stable
and levator resection
muscle and ptosis
sx
63/M No OS Choroidal folds Proptosis, LOM, mass LG and orbital No Bx Amyloidosis Stable
noted by optician/ close to orbital rim mass
12 m
57/M No OD Epiphora, Peripunctal conj mass, Peripunctal and N/A Bx, mini- Amyloidosis Stable
peripunctal conj punctual ectropion palpebral conj monoka
mass/NA stent
insertion
59/M Floppy eyelid, OD OSS/NA Thickened peripunctal conj, Bulbar and N/A Bx Amyloidosis Stable
diverticular pink bulbar conj nodule palpebral conj
disease
68/F DM, HT, impared OU Ptosis, OSS/12 m Ptosis, conj giant cobblestone Palpebral conj NA Bx Amyloidosis Rec
renal function papillae
58/M Primary OU ES, OSS/9 m Thickening of the lid, Palpebral conj Yes Bx Amyloidosis Stable
amyloidosis, inflamed conj
pancreatic
insufficiency
Kamal 46/F NA OS ES, ptosis, OSS/ Ptosis, thickened tarsus Upper tarsus, No Bx AL-amyloidosis NA
(2012) 24 m levator (k and j)
[49] muscle
291

123
 Table 1 continued
292

Author Age/sex Ocular or Eye Chief Clinical features/ Localization Sys Treatment Histopathology Outcome
(year) systemic complaint/duration CT feature A

123
antecedents (months)

35/F NA OU ES/12 m Mass in the tarsal Palpebral conj, No Inc bx AL-amyloidosis NA

area, ptosis levator muscle
Chee (2013) 54/M HT OU ES/36 m ES, LOM Upper and lower No Inc bx, upper Amyloidosis and Autologous
[50] eyelid blepharoplasty plasma cell myeloma stem cell
transplantation
Chakraborti 19/M No OU Ptosis OD/48 m Ptosis, yellowish Palpebral conj No Exc bx, Amyloidosis Stable
(2014) pink conj mass lower an upper crioterapy
[51]
Jacoby 69/M HT, Prostate OU Nodular lesion/ Nodular lesion in Lower and upper Yes Bx AL-amyloidosis (k), Chemotherapy.
(2014) cancer 120 m the eyelid eyelid, medial Waldenström Stable
[52] orbit macroglobulinemia
Batra (2014) 72/F HT, DM OS Orbital growing Ptosis, pinkish LG No Exc bx Amyloidosis Stable
[53] mass/36 m white mass in
the LG/calcif
Nair (2014) 32/M N/A OD Nodular mass/NA Nodular mass in Lower eyelid No Inc bx Amyloidosis Stable
[54] the eyelid
Murchinson 82/F Scirrhous OD Diplopia/2 m Enophthalmos, Right inferolateral No Bx AL-amyloidosis Stable
(2014) breast LOM orbit, lateral
[55] cancer rectus muscle
Suesskind 29/M Conj tumor OS Tumor growth, pain/ Salmon-colored Bulbar conj NA Bx Lipodermoid with NA
(2015) 3m tumor amyloidosis
[56] 44/M NA OS RSH/18 m Yellow thickening Bulbar conj No Bx Amyloidosis Rec
of conj
77/F NA OS Branch vein Papillomatous Inferior tarsal conj N/A Bx AL-amyloidosis (k and Stable
occlusion, alterations of j)
epiphora/NA conj
67/F NA OD OSS/NA Conj and Superior conj N/A Bx Amyloidosis Stable
episcleral
thickening
58/F NA OD OSS/NA Yellow pink Bulbar conj No Bx Amyloidosis NA
thickening of
conj
75/M NA OS Conj tumor, OSS/ Reddish conj Conj next to NA Exc bx Amyloidosis NA
1 week tumor semilunar fold
Int Ophthalmol (2016) 36:281–298
 Table 1 continued
Author Age/sex Ocular or Eye Chief Clinical features/CT Localization Sys Treatment Histopathology Outcome
(year) systemic complaint/duration feature A
antecedents (months)

Mora- 18/F No OS RSH/8 m Conj thickening, Bulbar conj No Inc bx Amyloidosis Stable
Horna yellowish subconj
(present) deposit
41/F Conj OS ES, ptosis/72 m Conj mass, ptosis Upper palpebral conj No Inc bx Amyloidosis Stable
amyloidosis
59/M No OU Conj mass, OSS/3 m Conj mass Bulbar and tarsal conj NA Inc bx Amyloidosis Stable
Int Ophthalmol (2016) 36:281–298

84/F HT OS Visual disturbance, Conj mass Bulbar conj No Inc bx Amyloidosis Stable
OSS/NA
63/F No OD ES, diplopia, pain/ Ptosis, ES, orbital mass, Superior orbit, lateral and NA Inc bx Amyloidosis NA
36 m oc dis, proptosis, superior rectus muscle,
LOM/calcif LG
73/F Trachoma, OD OSS/240 m Conj thickening Palpebral conj NA Inc bx Amyloidosis NA
rosacea, AR
69/F RA OD RSH, OSS/72 m Yellowish subconj Bulbar conj No Inc bx Amyloidosis Stable. Die after
deposit, subconj hem 13 years
65/M HT, DM OS Corneal ulcer/NA Salmon conj mass Bulbar and palpebral conj NA Inc bx Amyloidosis NA
22/F No OS OSS, ES/4 m Orbital mass, oc dis, LG No Exc bx Amyloidosis Rec and
calcification nasopharinx
involvement
40/F HT, migraine OS Eyelid mass, OSS/ Orbital mass, conj mass LG, bulbar and palpebral No Exc bx Amyloidosis Rec and frontal
48 m conj sinus
involvement
54/F No OS Eyelid mass, ptosis/ Conj mass, ptosis Upper and lower No Inc bx Amyloidosis Stable
60 m palpebral conj
56/F DM OD ES, OSS/36 m Conj mass Bulbar and palpebral conj NA Inc bx Amyloidosis NA
87/F RA, DM OS OSS, RSH/7 m Conj mass Bulbar conj NA Inc bx Amyloidosis NA
59/F No OD ES, OSS/6 m Eyelid mass Lower eyelid No Exc bx Amyloidosis Rec requiring
new sx

F female, M male, OD right eye, OS left eye, OU both eye, Sys A systemic amyloidosis, HT hypertension, RA rheumatoid arthritis, DM diabetes mellitus, MM multiple myeloma,
OHT ocular hypertension, NA not available, RHS recurrence, subconjunctival hemorrhage, ES eyelid swelling, OSS ocular surface symptom, hem hemorrhage, conj conjunctiva,
subconj subconjunctival, oc dis ocular displacement, LOM limited ocular movements, calcif calcification, LG lacrimal gland, Inc bx incisional biopsy, Exc excisional biopsy, Bx
biopsy, sx surgery, Rec recurrence, MRI magnetic resonance imaging, PPD purified protein derivative of mycobacterium tuberculosis
293

123
294
Evitar la Ceguera en México, I.A.P. Hospital ‘‘Dr.
Luis Sánchez Bulnes’’ during a period of 20 years and
analyze this information with the largest number of
cases with this diagnosis previously published in the
literature in the last 10 years.
Amyloidosis is a disease caused by extracellular
amyloid deposits [5]. The estimated incidence of AL-
amyloidosis is 3.2 per million per year and AA
amyloidosis 2.0 per million per year while the median
age for AL and AA amyloidosis is between 55 and
60 years [8].
Ophthalmologic involvement in the setting of
amyloidosis is very rare. Conjunctival amyloidosis
was reported in only five of 2455 conjunctival lesions
(0.2 %) [25]. Orbital amyloidosis was found in 22 of
6328 patients with orbital disease (0.3 %) [57].
The mean age of presentation in our study was
54.9 years, affecting more women than men (65.1 vs
33.7 %), and with a mean duration of symptoms of
32.4 months. These findings are comparable to those
reported by Leibovitch et al. [13]., who found in 24
cases a mean age of 57 years and also a female
predilection (62.5 %), with a mean duration of symp-
toms of more than 3 years.
According to the affected fibril protein, there are
several types of amyloidosis. The classic forms of
amyloidosis are light chain amyloidosis (AL) and
amyloid A protein amyloidosis (AA), previously
classified as primary and secondary, but it has long
been recommended that the latter designations should
not be used [3, 7]. Each one has been associated to
different conditions: AA amyloidosis with chronic
inflammatory conditions such as RA, spondyloarthri-
tis/psoriasis, inflammatory bowel disease, familial
Mediterranean fever or Sjögren’s syndrome; chronic
infections; neoplasms; or idiopathic causes, among
others [58]. On the other hand, AL-amyloidosis has
been related to MM, Waldenström’s macroglobuline-
mia or non-Hodgkin lymphoma [59, 60]. Fifteen
percent of patients with myeloma have symptomatic
AL-amyloidosis and up to 30 % may have incidental
deposits, which may become clinically significant
with improving long-term outcomes in myeloma [61].
In our study, immunohistochemistry was per-
formed to the biopsies of 25 patients; of these, 22
were classified as AL-amyloidosis (7 with only kappa
light chain variety, 7 with only lambda and four with
kappa and lambda; the rest with unspecified light
chain), 2 as AA amyloidosis and one as having both. In
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Int Ophthalmol (2016) 36:281–298
our review, of the 6 patients with myeloma, four were
AL-amyloidosis, which is a frequent association as
previously noted. The 3 patients with MALT lym-
phoma and the single cases of solitary osseous
plasmacytoma and Waldenström macroglobulinemia,
all plasma cell dyscrasias, also had AL-amyloidosis.
Of the patients with AA amyloidosis, one had an
underlying rheumatic disease that increases the risk of
developing it: RA. The incidence of RA in the setting
of AA amyloidosis is 12–21 % [58]. Nevertheless,
other 4 patients, one of them with AL-amyloidosis,
also had AR.
The clinical features of ocular amyloidosis vary
depending on the localization. In the case of conjunc-
tival and eyelid involvement, the clinical picture may
consist of eyelid edema, papules, and yellowish
subconjunctival plaques (crumbly, easily bleeding
and able to affect the entire surface of the palpebral
conjunctiva), signs of conjunctival irritation, lumps or
swellings and an eyelid ptosis [41].
In the group of 53 patients with superficial amyloi-
dosis of our study, we found similar demographic
characteristics and clinical features than those
reported in the review of 50 patients with conjunctival
amyloidosis by Demirci et al. [25] (Table 2). We
found ocular surface symptoms in almost half of our
patients that could be attributed to an alteration in
lacrimal film. In the majority of patients with
involvement of superior palpebral conjunctiva and/or
the levator muscle [7, 49], as well as with eyelid
swelling, we found ptosis, which can be explained by a
mechanical cause that can be resolved following
excision of the mass [62], or have a functional
pathogenesis if the levator or Müller muscle are
affected by the disease [41]. Vessel fragility due to
amyloid deposition within the wall of small blood
vessels can explain the subconjunctival and periocular
subcutaneous hemorrhages [21]. The latter should
raise the possibility of systemic amyloidosis, as shown
in the 2 patients in our study that had this clinical
presentation [63], as well as AL-amyloidosis, in which
this finding is almost pathognomonic but only occurs
in a third of all cases [61]. Trachoma has been
associated with amyloid deposit [25, 62]. We found 1
patient with this antecedent.
Regarding the group of 26 patients with deep
amyloidosis of our study, we found a similar distri-
bution regarding gender and age of presentation than
the cases reported in the review by Taban et al. [6].
Int Ophthalmol (2016) 36:281–298
Table 2 Comparison of the
main features of superficial
amyloidosis Male/female
Mean age (years)
Bilateral involvement
Signs and symptoms
Mass
Ocular surface symptoms
Ptosis
Subconjuctival hemorrhage
Systemic amyloidosis
predominance of women in 69.2 versus 67.7 % and
mean age of presentation of 56.6 versus 61.6 years.
The symptoms in deep amyloidosis could be more
evident than in the conjunctival variety due to its possible
involvement of extraocular muscles (though the tendons
of these muscles usually are spared), orbital fat and/or
lacrimal gland, causing a mass effect that can be
expressed as limited ocular movements, proptosis, ocular
displacement and ptosis, among other manifestations [6,
13, 27]. This can be supported by the mean duration of
symptoms of 18.2 versus 37.6 months in conjunctival
amyloidosis as it was shown in our study. Nevertheless,
in rare cases, it can be asymptomatic as in one of our
reviewed cases where the orbital involvement was
incidentally discovered on magnetic resonance imaging
(MRI) of the brain as part of a stroke evaluation [42].
Other rare forms of presentation are eyelid pigmentation
and enophthalmos as we found in our review [28, 55].
Four of the 26 cases with deep amyloidosis of our study
had systemic involvement (15.4 %).
Calcifications are frequent CT findings that can be
associated to this variety of amyloidosis as shown in 9
of the 26 patients (34.6 %). These calcifications could
represent phleboliths that probably result from amy-
loid deposition surrounding blood vessels, which
renders them susceptible to rupture from subsequent
thrombus formation [23].
Of the 83 cases of our review, only 4 presented with
combined involvement of superficial (periocular) and
deep (orbital) tissues. The predominant symptoms in
these patients were those related to a mass effect,
probably explained by the fact that these symptoms are
more evident. One of these 4 cases had systemic
amyloidosis (25 %).
The gold standard for diagnosis of periocular and
orbital amyloidosis requires a tissue biopsy that
295
Present study N = 53 Demirci et al. [25] N = 50
19/34 21/29
54.1 46.7
14 (26.4 %) 19 (38 %)
45 (84.9 %) 42 (84 %)
25 (47.2 %) –
16 (30.2 %) 15 (30 %)
9 (17 %) 16 (33 %)
8 (15.1 %) 3 (6 %)
exhibits the pathognomonic apple-green birefringence
and red–green dichroism after staining with Congo red
and viewing in intense unidirectional polarized light
[1, 5, 13]. CT and MRI are not diagnostic but are
important in localizing the involved orbital structures
[13]. In general, CT is more sensitive than MRI in
determining the calcific changes in the lesion content
and bone changes [46]. Nevertheless, MRI can help
add a more accurate anatomical definition of the
extension of the lesion [37].
Once amyloid has been found in a site specific for
localized amyloidosis, it is recommended to screen for
amyloid in another site of the body with a tissue
biopsy, such as subcutaneous fat (sensitivity of up to
90 %, specificity of almost 100 %), rectum (sensitiv-
ity of 80 %), bone marrow (sensitivity of 60 %), or
salivary glands, before diagnosing localized amyloi-
dosis [8]. Immunohistochemistry is useful for identi-
fying different amyloid proteins, thus orientating
toward possible associations and prognosis. Also, a
systemic evaluation at the time of diagnosis should be
done with the following baseline investigations:
complete blood count, urine analysis, and serum
electrolytes including Ca2? levels, liver function tests,
b2-microglobulin, prothrombin time and activated
partial prothrombin time, Ig levels, 24-h urinary
protein, Bence Jones protein, electrocardiography
and skeletal survey [25].
Although radionuclide imaging studies using tech-
netium-labeled aprotinin or iodinated serum amyloid
P (SAP) component scans can be used to detect and
identify the distribution of amyloid in systemic
amyloidosis, these are not a substitute for histologic
characterization of amyloid deposits and are not
widely available [59]. Scintigraphy with iodinated
serum amyloid P (SAP) shows specific uptake in the
123
296
liver, spleen, kidneys, adrenals, bone marrow, and
joints (sensitivity of about 90 % in AL- and AA-
amyloidosis, specificity of 90 %) [8]. The heart cannot
be visualized with SAP technique. On the other hand,
aprotinin scintigraphy with technetium Tc 99 m has
been used successfully for the identification of cardiac
involvement in AL-amyloidosis [8, 59].
Treatment for AA amyloidosis is aimed at decreas-
ing serum amyloid A protein levels to normal basal
values (\3 mg/L). The only way to achieve a normal
basal serum value of amyloid A protein is by complete
suppression or eradication of the underlying chronic
inflammatory disease [8].
The aim of treatment in AL-amyloidosis is eradi-
cating the fibril precursor protein by suppressing
production of free light chains by targeting the
underlying clonal plasma/B cell dyscrasia. This can
be achieved with chemotherapy or high-dose melpha-
lan followed by autologous stem cell transplantation in
eligible patients [8, 61].
Surgical debulking or excision is the primary
treatment for localized amyloidosis. However, despite
careful debulking, recurrences are known to occur and
are considerably higher in orbital disease than in solely
conjunctival involvement (29 and 15 %, respectively)
[7]. Nevertheless, in our study, we found recurrences
or requirement of new surgeries after diagnosis in
24.5 % of the patients with superficial amyloidosis
and in 23.1 % of the cases with deep amyloidosis. This
could be attributed to the fact that the follow-up period
was variable and, in some cases, the information
regarding the outcome was not available.
Other reported treatments for localized amyloidosis
are cryotherapy and radiotherapy. Cryotherapy may be
therapeutic for conjunctival amyloidosis because it
disrupts the blood supply to the amyloid deposits.
Surgical debulking before cryotherapy may be bene-
ficial in allowing the freezing to reach the deeper
blood supply [64]. In our study, 3 patients received this
treatment in combination with prior excisional biopsy,
with no recurrences. Other treatment modalities
include CO2 laser vaporization with good results and
lower risk of pathological scarring [41].
Radiotherapy may be useful as an adjunct to
surgical debulking of deep orbital disease when
surgical clearance may not be complete and further
recurrence is likely. It may also have a role as sole
treatment by eradicating a localized clone of plasma
cells that produce antibodies that act as amyloid
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Int Ophthalmol (2016) 36:281–298
precursors [34]. In our study, 3 patients with deep
disease and one with superficial disease received this
adjuvant treatment after surgical intervention. Two of
these patients had localized amyloidosis in association
with lymphoproliferative disease, one with plasmacy-
toma and the other one with clonal infiltration of
plasma cells [29, 30, 34], all of them with improve-
ment of the disease.
Conservative management could be an alternate
choice in the treatment of orbital and conjunctival
amyloidosis. This can be achieved with the use of
lubricants and bandage contact lens [7, 25]. If the
patient is comfortable and there is no progression of the
amyloidosis, it is acceptable to observe the patient [7].
As a conclusion, amyloidosis is a rare disease,
especially when it affects the periocular and orbital
tissues. It can present with a variety of symptoms and
signs, depending on the localization and extension of
the involvement. It is important to always determine
the specific type of amyloid involved even in the cases
where it can be assumed because of the medical
history and clinical picture. Systemic disease should
always be investigated. Once all of this is established,
we can be able to take decisions regarding treatment
modalities, which will affect the prognosis of each
particular case.
Compliance with ethical standards
Conflict of interest The authors have no financial or conflicts
of interest to disclose.
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