Subspeciality-Oculoplasty
Table 8: An ideal conjunctival substitute the socket should have the following
• Easily available, stable characteristics:
• Elastic to enable tension-free movement and lid closure while integrating into
• Easily available and stable
the host conjunctiva without causing inflammation
• Resistant to an inflammatory environment such as in patients with OCP or SJS • Elastic to enable tension-free
• Act as a scaffold to guide tissue formation movement and lid closure
while integrating into the host
mucous membrane can serve as an used to increase the vascularity of the conjunctiva without causing
alternative for bulbar conjunctiva but socket. The superficial temporal artery inflammation.
is less suitable for fornix reconstruction supplies the temporalis fascia and this
as it contracts more than full-thickness can be brought into the socket through • Resistant to an inflammatory
mucosa. Mucosa harvested from the the lateral canthus by forming a pedicle environment such as in patients
hard palate is the stiffest oral graft and flap. Once the flap takes up and the with OCP or SJS.
contracts the least but is slightly more vascularity improves, the fornices can
difficult to obtain compared to labial be formed using a mucous membrane • Act as a scaffold to guide tissue
mucosa. graft. formation.
c. Amniotic membrane Graft
The lower lip is everted with a traction Human amniotic membrane (AM) - The most promising groups of materials
sutures. The area for the graft is marked the innermost layer of the placenta, for tissue engineered conjunctiva are:-
out taking care to avoid the frenulum contains several cytokines and
below and to be a couple of mm away growth factors and promotes cell • Synthetic polymers- The poly
from the muco-cutaneous junction. growth and inhibits inflammation (lactide- co-glycolide) (PLGA) or
Larger grafts can be harvested from the and fibrosis has been described for poly-e-caprolactone (PCL) is the
buccal mucosa, however the retrieval socket reconstruction. However, it is closest match because of their
is more cumbersome due to decreased not recommended in large defects as highly consistent quality. They
exposure of that area. The marked AM tends to dis-integrate within 7-10 are produced easily under GMP
area is then injected with xylocaine days hence cannot serve the purpose conditions and with tuneable
with adrenaline which facilitates the of surface augmentation. It can be material properties. Unlike
removal of mucosa and also decreases however, used for smaller conjunctival biomaterials derived from a human
the bleeding. The graft is removed from defects (1-2mm) during socket. or xenogeneic source, they are free
below upwards so that the bleeding does Adjuvants treatment for surface of the risk of disease transmission22.
not obscure the field. The defect can be contracture:-
either sutured with 6-0 vicryl sutures • Mitomycin C (MMC) • Artificial collagen matrices- The
or covered with a amniotic membrane The augmentation with topical plastic compressed collagen (PCC)
graft for faster healing. Pressure dressing mitomycin C (MMC) application during gels offer good biomechanical
may be given to stop oozing. It is better reconstruction surgery for contracted properties and conjunctival
to avoid too much cautery as this can socket improves the outcome16. epithelial cells cultured on PCC
cause scarring and distortion of the lips. Surgical sponges soaked in 0.2 mg/ml gels are able to forma confluent
Trimming of the fat from the graft is MMC under the conjunctival flaps for and tightly connected epithelial
very important, as the chances of failure 5 min and reported a significant deeper cell layer17. Recently, experiments
to uptake and vascularisation are more fornix in MMC-treated eyes and that using an in vivo conjunctival
with thick grafts. Post-operatively the 75% of these patients could maintain defect model, PCC showed high
patient is given systemic and topical the prosthesis after 12 months. stability and good integration into
antibiotic and betadine gargles for the Recent advances in management of the host tissue with the formation
donor site. contracted socket: of a multi-layered epithelium
Engineered conjunctiva: An ideal including secretory active goblet
• Contracted avascular socket conjunctival substitute for lining cells23. No relevant inflammatory
Graft uptake is poor in such sockets due reaction, signs of scarring such as
to compromised blood supply. Such myofibroblast persistence or fornix
sockets e.g. Post radiation socket needs shortening were observed at the
to be vascularised before grafting. For implantation site.
this temporalis muscle and fascia can be
• Decellularized tissues with
or without subsequent
recellularization- During
decellularization, donor cells and
antigens are completely removed
while the ECM composition and
tissue-specific 3D architecture
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Subspeciality-Oculoplasty
are preserved18. Tissues such as over it. Modifications in the prosthesis Craniomaxillofac Surg. 1999;27:72–6.
amniotic membrane, skin and may be required in contracted socket
conjunctiva have been assessed for cases. Spectacles to camouflage the 6. Tse DT. Inventor; University of Miami
de- and recellularization and have defect can be very useful in obtaining a (Miami, FL) assignee. Integrated rigid
in some cases been progressed to decent cosmetic outcome. fixation orbital expander. US patent
clinical application. 6,582,465 B2 June 2003.
Commercially available acellular Exenteration prosthesis/ Orbital
human (Alloderm® or DermaMatrix®) prosthesis 7. Tse DT, Pinchuk L, Davis S. Evaluation
or porcine (Permacol® or Tarsys®) of an integrated orbital tissue expander
cadaveric dermis has been reported for These are indicated in exenterated in an anophthalmic feline model. Am J
skin and ocular socket reconstruction orbit and patients with severe degree Ophthalmol. 2007;143(2):317–27.
or to correct lower lid retraction19-21. of socket contracture not amenable
Alloderm® is also used to cover exposed to reconstruction. After the complete 8. Tse DT, Abdulhafez M, Orozco MA, Tse
orbital porous implants. epithelialization of the socket, the JD, Azab AO, Pinchuk. Evaluation of
patient can be fitted with an oculofacial an integrated orbital tissue expander
prosthesis. The traditional method in congenital anophthalmos: report of
of prosthesis construction involves preliminary clinical experience. Am J
taking an impression of the orbit with Ophthalmol. 2011;15(3):470–82
a plaster cast to make a mould, with
Eyelid defects in contracted socket which a silicone template is made and 9. Jordan DR, Klapper SR. Evaluation
painted to resemble the normal eye. The and management of the anophthalmic
Surface contracture related prosthesis can be attached to thicker socket and socket reconstruction. In:
eyelid defects like entropion and glasses frame to help camouflage the Smith and Nesi’s ophthalmic plastic and
lagophthalmos can be significantly prosthesis-skin interface or directly reconstructive surgery. 3rd ed. Berlin:
corrected with mucus membrane attached to periorbital skin with Springer; 2012. P
skin adhesive or magnetic posts24.
grafting. Persistent entropion even after With advancements in 3D-printing 10. Tucker SM, Sapp N, Collin R. Orbital
surface augmentation may require, technology, custom-printed prostheses expansion of congenitally anophthalmic
spacer grafts in the involved eyelid. at a lower cost than the traditional socket. Br J Ophthalmol. 1995;79:667–71.
Cartilage graft harvested from the post methods are made. Patients are required
auricular cartilage/ hard palate or nasal to wear polycarbonate glasses to protect 11. Chen D, Heher K. Management of
septal cartilage is preferred. the remaining eye, with life-long the anophthalmic socket in pediatric
monocular precautions along with the patients. CurrOpin Ophthalmol.
Lower lid laxity in cases of long-term use prosthesis. 2004;15:449–53.. 1131–73
of a bulky prosthesis can be corrected
by lid tightening procedures like Lateral References 12. Leatherbarrow B. Oculoplastic surgery.
tarsal strip. 1. Krishna G. Contracted sockets—I 2nd ed. London: Informa; 2011.
Anophthalmic ptosis is an important (aetiology and types). Indian J 13. Kaltreider SA. The ideal ocular
component of the post enucleation Ophthalmol.1980;28(3):117–20. prosthesis: analysis of prosthetic
socket syndrome and is mostly 2. Gundlach KKH, Gutoff RF, Hingst VHM, volume. Ophthal PlastReconstr Surg.
aponeurotic in nature. Mild ptosis et al. Expansion of the socket and orbit 2000;16:388–92.
can be managed with prosthesis for congenital clinical anophthalmia.
modification. In severe ptosis, levator PlastReconstr Surg. 2005;116:1214–22. 14. Kaltreider SA, Lucarelli MJ. A simple
surgery may be required. Levator 3. Dunaway DJ, David DJ. Intraorbital algorithm for selection of implant
surgery with adjustable sutures is tissue expansion in the management size for enucleation and evisceration.
preferred as anophthalmic ptosis is of congenital anophthalmos. Br J Plast
known to be unpredictable even in the Surg. 1996;49:529–35. OphthalPlastReconstr Surg.
best of hands. 4. Sinclair D, Dangerfiled P. Nervous 2002;18:336–41
system. In: Sinclair D, Dangerfield P,
Prosthetic Rehabilitation editors. Human growth after birth. 15. Yoon JS, Lew H, Kim SJ, Lee SY. Exposure
Oxford: Oxford University Press; 1998. p. rate of hydroxyapatite orbital implants
Customized ocular prosthesis is fitted 87 a 15-year experience of 802 cases.
into the socket after the volume and 5. Weise KG, Vogel M, Guthoff R, Ophthalmology. 2008;115(3):566–72.
surface of the contracted socket is taken Gundlach K. Treatment of congenital
care off. Prosthesis can be fitted into anophthalmos with self-inflating 16. Mandour SS, Elmazar HM, Marey
the socket 4-6 after the reconstructive polymer expanders: a new method. J HM, Rahman AKA, Sakr RA. Mucous
surgery and after the socket membrane grafting augmented with
inflammation and edema has subsided. topical mitomycin c application in
Commonly used customized prosthesis contracted socket repair surgeries. J.
are made of acrylic or silicone with Ocul. Pharmacol. Ther. 2016;32(10):691–
structures like iris and vessels painted 94.
17. Drechsler C, Kunze A, Kureshi A, Grobe
G, Reichl S, Geerling G, Daniels J, Schrader
S. Development of a conjunctival
tissue substitute on the basis of plastic
compressed collagen. J. Tissue Eng.
Regener. Med. 2015;11(3):896–904.
52 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times
Subspeciality-Oculoplasty
18. Hussey GS, Dziki JL, Badylak SF. N, Geerling G. Decellularized porcine technique for the rehabilitation of the
Extracellular matrix-based materials for derived membrane (tarsys®) for exenterated orbit. Arch Ophthalmol.
regenerative medicine. Nat. Rev. Mater. correction of lower eyelid retraction. 1991;109(7):1032–8.
2018;3:159–73. Orbit. 2012;31(3):187–89.
Corresponding Author:
19. Lee EW, Berbos Z, Zaldivar RA, Lee MS, 22. Hussey GS, Dziki JL, Badylak SF.
Harrison AR. Use of dermamatrix graft Extracellular matrix-based materials for Dr. Sima Das MS
in oculoplastic surgery. Ophthal. Plast. regenerative medicine. Nat. Rev. Mater. Dr. Shroff’s Charity Eye Hospital, Drayaganj,
Reconstr. Surg. 2010;26(3):153–54. 2018;3:159–73. New Delhi, India
20. Shorr N, Perry JD, Goldberg RA, Hoenig 23. Witt J, Borrelli M, Mertsch S, Geerling
J, Shorr J. The safety and applications G, Spaniol K, Schrader S. Evaluation
of acellular human dermal allograft in of plastic compressed collagen for
ophthalmic plastic and reconstructive conjunctival repair in a rabbit model.
surgery: A preliminary report. Ophthal. Tissue Eng. Part A. 2018;25:1084–95.
Plast. Reconstr. Surg. 2000;16(3):223–30.
24. Nerad JA, Carter KD, LaVelle WE, Fyler
21. Borrelli M, Unterlauft J, Kleinsasser A, Brånemark PI. The osseo integration
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Subspeciality-Oculoplasty
Orbital Trauma
Maya Hada MD1, Nikhil Agarwal MD2
1. Oculoplastic and Ocular Oncology Services, S.M.S. Hospital, Jaipur, Rajasthan, India
2. A.I.I.M.S, Bhatinda, Punjab, India
Orbital trauma is a significant public Figure 1a: Clinical photograph of 8 year old boy, post tennis ball injury to right orbit. b:
health issue, and it may lead to lesions CT scan coronal section shows fracture of the right orbital floor with inferior rectus muscle
of the globe, optic nerve, and adnexa, entrapment. c: Restriction of supraduction is present in right eye. d: CT scan saggital section
ranging from the relatively superficial showing the “tear-drop sign”.
to vision-threatening complications.
Orbital and periorbital injuries may edema (can be absent in white-eyed the V2 distribution, including
vary in severity. This article presents blowout) the cheek, lower eyelid, upper
a brief overview of the evaluation and • Vertical Diplopia with limitation of lip, upper gums, and teeth on the
management of orbital and periorbital upgaze, downgaze, or both (Figure affected side.
injuries. 1) - Due to the entrapment of the
IR muscle (The larger and more • Oculocardiac reflex – In white-
Orbital Fractures comminuted the fracture, the less eyed blow out fractures with IR
a. Orbital floor fractures likely entrapment and diplopia are entrapment, an attempt to move
to occur). Forced duction test shows the eye may cause increased vagal
Orbital floor fractures account for 65- restriction as well as there may be tone leading to oculocardiac
80% of all orbital fractures. The maxilla increased IOP in upgaze > primary reflex, which manifests as severe
in posteromedial aspect of the orbital position. bradycardia or heart bock, syncope.
floor is the thinnest part of the floor • Enophthalmos and ptosis of the An urgent surgical intervention is
and is the commonly fractured site. globe - Large fractures (typically warranted in such cases.
Retropulsion or hydraulic theories have more than 50% of the entire floor),
been proposed for the pathophysiology Soft tissue prolapse into maxillary Management of orbital floor fractures:
of a floor fracture. In hydraulic theory, sinus. Enophthalmos is more Once it is established that a patient
trauma with a significant impact on apparent when edema subsides. has an orbital fracture that does not
the globe causes retropulsion force that • Anaesthesia over the cheek – Floor need emergent surgical intervention,
results in blowout fracture. In buckling fractures involving the infraorbital medical management should be
theory, traumatic forces are conducted canal can result in numbness of initiated. A course of oral steroids of 1
along the orbital rim to the orbital mg/kg per day for a few days help reduce
bones, resulting in fractures. swelling and scar tissue development.
Patients in pediatric age group may
present with ‘white-eyed blow out
fracture’. These patients show minimal
signs but present with marked
restriction in supraduction and
infraduction due to muscle entrapment.
This is due to the higher elasticity of
bones. The entrapped fractures are
associated with bradycardia due to the
triggering of oculocardiac reflex. Patient
should be evaluated and palpated
for crepitus, displaced fracture, and
restriction of extraocular movements.
Clinical signs are as follows:
• Eyelid sign – Ecchymosis and
54 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times
Subspeciality-Oculoplasty
Adjunctive use of analgesics and nasal Table 1: Clinical recommendations for repair of Isolated Orbital Floor
decongestants can be part of initial Fractures1
medical management. Guidelines for
surgical management of Orbital floor Intervention Scenario
fractures are given in Table 1.
Immediate Diplopia present with CT evidence of an entrapped muscle or
b. Medial wall fracture periorbital tissue associated with a nonresolving oculocardiac
reflex: bradycardia, heart block, nausea, vomiting or syncope*
The thin ethmoidal bone, Lamina “White-eyed blow-out fracture.” Young patients (< 18 y),
papyracea, is fractured in medial wall history of periocular trauma, little ecchymosis or edema (white
fracture which may be associated with eye), marked extraocular motility vertical restriction, and CT
entrapment of medial rectus. Clinical examination revealing an orbital floor fracture with entrapped
signs include: muscle or perimuscular soft tissue Early enophthalmos/
hypoglobus causing facial asymmetry
• Horizontal diplopia – Unlike floor
fractures with vertical diplopia Within two Symptomatic diplopia with positive forced ductions, evidence
weeks of an entrapped muscle or perimuscular soft tissue on CT
• Orbital emphysema – Fracture into examination, and minimal clinical improvement Large floor
the adjacent sinus allows sinus air fracture causing latent enophthalmos Significant hypo-
and bacteria into the orbit. Patient ophthalmos Progressive infraorbital hypesthesia
should be instructed to avoid nose
blowing. Emphysema may be Observation Minimal diplopia (not in primary or downgaze), good ocular
significant enough to cause optic motility, and no significant enophthalmos or hypo-ophthalmos
nerve compression and loss of
vision. In such scenario of acute *Burnstine, M. A. (2003). Clinical recommendations for repair of orbital facial fractures. Current
pneumo-orbita, an urgent orbital Opinion in Ophthalmology, 14(5), 236–240.
paracentesis can be sight-saving.
through the fronto-nasal recesses d. Orbital apex Fracture
• Orbital hemorrhage – More dramatic as clear fluid rhinorrhea. Fracture
than fracture floor due to lack of the at cribriform plate can also damage Orbital apex fractures involve the optic
natural drainage afforded by a floor the olfactory nerves leading to canal and the superior and inferior
fracture anosmia. orbital fissures. This type of fracture
can cause traumatic optic neuropathy,
• Enophthalmos – Sufficiently large • Restricted up-gaze and ptosis multiple cranial neuropathies, and
medial wall fracture allows - Secondary to the inward long-term visual morbidity.
prolapse of enough orbital tissue to displacement of the levator/
create enophthalmos. superior rectus muscle complex e. Lateral wall fracture
by the bony fracture plate
Naso - Orbital - Ethmoidal (NOE) and associated subperiosteal Lateral wall is the most substantial
fractures usually result from the face hematoma. wall, and the fractures are rare.
striking solid surfaces and involve However, severe injuries can
frontal process of the maxilla, the • Hypoesthesia of CN V1 – Crack cause tripod fracture known as the
lacrimal bone, and the ethmoid bones through the supraorbital notch or Zygomatico-maxillary complex (ZMC).
along the medial wall of the orbit. These foramen creating numbness across If the zygoma is dislocated, a tender
may present as depressed bridge of the the forehead and scalp. rim step-off or separation can be felt,
nose and traumatic telecanthus. either inferiorly or laterally. Other
• Hypo-ophthalmos and pulsatile clinical signs include:
c. Orbital roof fracture exophthalmos - Orbital floors
tend to blow out and roofs tend to • Malar flattening and increased
Roof fractures are usually caused by blow in because the orbit is more facial width. – Dislocation results in
blunt trauma or projectile missile compressible than the brain. As significant distortion of the cheek.
injuries. Symptoms and signs are as the bony fracture plate dislocates Lateral canthal dystopia may be
follows: into the orbit, displacing the present.
orbital contents anteriorly causing
• Epistaxis, CSF rhinorrhea and exophthalmos and inferiorly • Dysesthesia of cranial nerve V2
anosmia - Roof fractures extend to leading to hypo-ophthalmos. Open – Involving ipsilateral teeth and
the very thin bones of the ethmoid connection to the pulsatile ICP gums.
and cribriform plates. If dura is causes the globe to pulse, best seen
torn in these areas, CSF can drain during supine position. • Trismus and malocclusion. Large
from the anterior cranial fossa and displaced fractures may require
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Subspeciality-Oculoplasty
Figure 2a: Clinical photograph of 16 year old male, showing abaxial proptosis and Shearing forces (blunt trauma) lead to
inferior globe dystopia of left eye post trauma. b: CT scan, coronal section showing boat rupture of diploic veins, which traverse
shaped hyperdense collection beneath the periosteum of superior orbital wall, displacing the subperiosteal space. Distension
the globe inferiorly. c: CT scan axial section showing small fracture of the medial orbital of space leads to further separation
wall associated with hyperdense collection beneath the periosteum of medial wall of orbit of the periosteum from underlying
extending till posterior orbit. d: Clinical photograph of the patient post needle drainage of the bone, tearing more bridging vessels,
subperiosteal hematoma (inset) and resolution of proptosis. resulting in bilenticular shaped
hematoma. Acute hematoma can lead
Figure 3a: CT scan coronal section showing fractures of multiple orbital walls and a to visual compromise due to optic nerve
foreign body in the inferolateral orbit with presence of central hypodensity (yellow arrow) compression. Urgent drainage (needle /
suggestive of air inside the wood. b: CT scan axial section showing linear track (red arrow) surgical exploration) is warranted in
of the hypodensity inside the wooden foreign body. such cases (Figure 2).
open reduction with fixation with and subperiosteal space. Orbital Orbital Compartment syndrome
titanium plates and screws. subperiosteal hematoma is a collection Orbital compartment syndrome is a
Orbital Hemorrhage of blood within the potential space rare but critical condition that can
Post traumatic orbital hemorrhage between the periosteum and the bones occur in a trauma setting when blood
may occur in three locations – of the orbit. The most common location or air is trapped in the closed orbital
intraconal space, extraconal space is a superior and medial orbit involving compartment. Compartment syndrome
the orbital plate of the frontal bone. should be suspected in any patient
who has suffered orbital trauma that
presents with pain, decreased visual
acuity with relative afferent pupillary
defect, proptosis, elevated intraocular
pressure, tense lids, and adnexa,
chemosis and possibly decreased ocular
movements. Lateral canthotomy and
cantholysis.
Orbital foreign body
Foreign bodies made of iron, copper,
wood, vegetative material, or those
causing penetrating injury to adjacent
structures need urgent surgical removal.
Foreign bodies made of inert materials
like should be treated conservatively
with observation, especially if the
patient is asymptomatic and/or the
foreign body is in a difficult to access
orbital location.
Intraorbital Foreign Body may enter
the orbit either by traversing between
the globe and the orbital wall or by
double perforation of the globe. These
foreign bodies can be composed
of organic or inorganic materials.
Organic foreign bodies include wood,
vegetative material, inorganic can be
either metallic or inert material like
glass, gold, silver, platinum, porcelain,
plastic, sand, cilia, or rubber. CT scan
is the imaging modality of choice.
Though metallic foreign bodies
can be easily seen on thin slice CT,
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Subspeciality-Oculoplasty
removal of orbital foreign bodies to
avoid any additional trauma to adjacent
orbital structures.
References
1. Burnstine, M. A. (2003). Clinical
recommendations for repair of orbital
facial fractures. Current Opinion in
Ophthalmology, 14(5), 236–240.
2. Fulcher, T. P., McNab, A. A., & Sullivan,
T. J. (2002). Clinical features and
management of intraorbital foreign
bodies. Ophthalmology, 109(3), 494–
500.
Corresponding Author:
Figure 4: Management protocol for retained Intra Orbital Foreign Bodies (IOrFB)2.
presence of wooden foreign bodies is any associated orbital complications Dr. Maya Hada MD
indicated by linear hypodensity inside caused by foreign body (Figure 4). Oculoplastic and Ocular Oncology Services,
the wood, which suggests air (Figure Tracking the entry wound via an S.M.S. Hospital, Jaipur, Rajasthan, India
3). The management of intraorbital anterior orbitotomy by retraction and
foreign body (IOrFB) depends on the dissection along the path of trajectory
composition, location in the orbit and is the preferred method for surgical
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Subspeciality-Oculoplasty
Animal Bites in Periocular Areas
Asha Samdani MD, DNB, FICO1, Gunjan Saluja MD2, Rachna Meel MS2
1. Centre for Sight to the affiliation, Centre for Sight, Banjara Hills, Hyderabad
2. Oculoplasty, Tumor & Pediatric Ophthalmology Services,
Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
Introduction bite wounds and scenarios that increase The management protocol after initial
risk of the same. triage include :
Animal bites constitute a small but
significant percentage of emergency Microbiology of animal bites. 1) Primary wound toilet
admissions worldwide. Animals Bacterial profile of infected dog 2) Anti Rabies Prophylaxis
commonly responsible for bites include and cat bite wounds comprises of 3) Infection control using antibiotics
dogs, cats, horses, rabbits, rats, and Pasteurella multocida, Staphylococcus 4) Wound repair
humans. (1,2) Dog bites constitute aureus, Streptococcus viridans, Immediate thorough cleaning and
60–80 % while cat bites constitute– Capnocytophaga canimorsus, and oral washing of the wound with soap and
20–40 % of all animal bite injuries (3). anaerobes. Infected human bites yield water is recommended. At first contact,
Children are often the target of animal a similar spectrum of bacteria except primary wound toilet should must
attacks. Facial injuries constitute nearly for Pasteurellae, C. canimorsus and be carried out using copious wound
10–15 % of all animal bite trauma. sometimes Eikenella corrodens. In a irrigation for at least 15 minutes
Central face (eyelids, nose and lips) is study analysing infection rates in bite followed by application of viricidal
more commonly involved. Open globe wounds, it was found that infection rate agents like alcohol (400-700ml/L) or
injuries are rarely seen. Periocular bites for crush wounds, punctured wounds betadine
usually cause eyelid lacerations with or and wounds greater than 3 cm was 3
without, lacrimal system involvement. times higher than for all other wounds. Anti Rabies Prophylaxis
Lower canaliculus is most commonly (6) Dog bite injuries over the head,
affected due to the lateral traction face, and neck are classified as Class
exerted during dog bite.(4, 5) Gram-negative rods like III injuries with a very high risk of
Capnocytophaga canimorsus and transmission of rabies. This warrants
Eyelid laceration due to periorbital Pasteurella multocida can cause both local treatment of the wound and
animal bite are may be challenging serious infections with shorter complete post-exposure prophylaxis
to repair owing to large size and loss incubation periods, especially in measures including immunoglobulin
of tissue architecture secondary to immunocompromised. These infections and vaccination.(10)
crushing element of the bite. Early and can be complicated by meningitis,
accurate reconstruction by a trained septicaemia followed by disseminated Rabies Immunoglobulin (RIG)
oculoplasty surgeon is desirable intravascular coagulation syndrome, WHO recommends that the total dose
when lacerations are large, there is renal failure and peripheral gangrene. should not exceed quantities/volume of
imminent risk of tissue loss, there is The mortality of C. canimorsus RIG: 20 IU/ kg for Human RIG (HRIG)
corneal exposure or there is canalicular septicaemia is about 23-31%.(7,8) or 40 IU/ kg of Equine RIG (ERIG). If
involvement. Apart from the surgical the calculated dose is insufficient to
challenge that eyelid dog bites pose, Management of periocular infiltrate all wounds, sterile saline may
risk of rabies and bacterial infections animal bite be used to dilute it 2 to 3 fold to permit
from dog bite also needs to be addressed Burroughs et al. have very succinctly thorough infiltration. If RIG was not
There is no universal consensus on the presented the “Rule of 50s” for dog bite administered when vaccination was
timing of repair. While early repair injuries, which state that ≤50 % of all begun, it can be administered up to
offers better cosmetic and functional dog bites leave significant scarring, seven days after the administration of
outcomes, delayed repair is advocated ≤50 % infection rate reduction with the first dose of vaccine. RIG should not
to reduce risk of contracting rabies. prophylactic antibiotics, and ≤50 be administered in the same syringe
Bacterial infections are more likely if % wounds are culture positive for as the vaccine and no more than the
the wound toilet is delayed. One must pathogens (9)
be familiar with signs of infection in
58 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times
Subspeciality-Oculoplasty
recommended dose should be given b) Delayed presentation beyond 8 Figure 2: A large eyelid laceration due to
as this may suppress production of hours dog bite injury.
antibodies.
c) Large wounds transmission. There are no clear
Anti Rabies vaccine (ARV) d) Wounds with hematoma guidelines regarding primary vs
Modern anti rabies vaccines like Human e) Cat bites secondary repair in dog bites as there
Diploid Cell Vaccine (HDCV), Purified f) Puncture wounds as it is difficult to is a potential risk of acquiring rabies.
Chick Embryo Cell Vaccine (PCECV), In eyelid lacerations with canalicular
Purified Verocell Rabies Vaccine cleanse and debride these wounds involvement, an early intervention is
(PVRV) & Purified Duck Embryo g) Dog bite in immunocompromised imperative for achieving canalicular
Vaccine (PDEV) must be administered patency(Figure1) (11,12) Hence in such
as per WHO recommendations. patients. cases primary repair may be considered
The vaccination must be started Amoxicillin/clavulanic acid combina- for better surgical outcomes with an
immediately (in category II & III tion provides broad spectrum coverage explained risk of contracting rabies.
exposures) irrespective of the status and is the most commonly used antibi- In large eyelid lacerations with risk of
of the biting animals. It can be otic for prophylaxis in animal bites.In significant tissue loss (Figure 2) or risk
administrated either by intramuscular cases with wound infection repair must of corneal exposure, minimal loose
(Essen regimen - on 0, 3, 7, 14, 28 days) be delayed and carried out after the in- sutures can be passed primarily with
or intradermal regimens (Updated Thai fection is controlled with antibiotics. an aim of appropriate tissue alignment
Red Cross Regimen : 2-2-2-0-2) Primary repair vs secondary thus reducing tissue loss, corneal
repair exposure and consequent morbidity.
The 5 dose Intramuscular Regime Careful and thorough wound toilet, RIG infiltration into the wound must
(Essen) : One dose of the vaccine should disinfection and debridement is be performed a few hours before the
be administered on days 0, 3, 7, 14 and extremely important to reduce the suturing as advised by WHO.(14)
28 is given in the deltoid region or, in risk wound infection and rabies
small children, into the antero-lateral Points of clinical importance
area of the thigh muscle. a) Pre-op • Primary wound toilet should
Intra dermal Regimen (Updated Thai b) Post-op include copious wound irrigation
Red Cross Regime : 2-2-2-0-2): Purified Figure 1: a) Pre-op and b) post-op of a lid for at least 15 minutes followed by
chick embryo cell rabies vaccine laceration caused by dog bite treated by application of viricidal agents like
(PCECV) & different brands of Purified primary closure. The patient is on follow- alcohol (400-700ml/L) or betadine.
vero cell rabies vaccine (PVRV) are up of 6 months with no rabies infection risk. (13)
approved for use through intradermal Picture credits: Neha Yadav • Periocular injuries being category 3
route in the country by Drug Controller injuries, RIG local infiltration into
General of India (DCGI). In this regimen the wound is of utmost importance.
0.1 ml of vaccine is administered
intradermally on each deltoid region on
days 0, 3, 7 & 28.
Antibiotic prophylaxis
Antibiotic therapy is not routinely
indicated in all wounds caused by
animal bites. Similar infection rates
have been observed with primary repair
compared to secondary repair in various
studies reported in literature.(6)
Antibiotics are advised in case of
infected wounds or wounds with
increased risk of infection. Following
factors are associated with an increased
risk of wound infection
a) Crush injuries with resultant tissue
devitalization
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Subspeciality-Oculoplasty
• If wound suturing is necessary Int J Oral Maxillofac Surg. 2005;34(5): controlled trial. Injury. 2014 Jan
in any case, local infiltration of 464-472. doi:10.1016/j.ijom.2005.04.001 1;45(1):237-40.
RIG should be ensured before 13. Park K. Rabies. Park’s Textbook of Preventive
suturing. A delay of few hours 7. Hermann CK, Hansen PB, Bangsborg and Social Medicine. Vol. 22. Jabalpur
after infiltration is preferable as it JM, Pers C. Bakterielle infektioner som (India): Bansaridas Bhanot publication;
helps in diffusion of antibodies into komplikation til hundebid [Bacterial 2013. pp. 251–6.
tissue.(13,14) infections as complications of dog bites]. 14. World Health Organization. Rabies -
Ugeskr Laeger. 1998;160(34):4860-4863.) Bulletin - Europe. Rabies information system
References of the WHO collaboration centre for rabies
1. MacBean CE, Taylor DM, Ashby K. 8. Tjong Joe Wai R, van Zeijl JH. Infecties surveillance and research. [cited 2016 Jan
door Pasteurella multocida: door 14]. Available from: http://www.who-rabies
Animal and human bite injuries in de hond of door de kat gebeten? bulletin.org/about_rabies /classification.
Victoria. 1998–2004. Med J Aust. [Pasteurella multocida infections: bites aspx
2007;186(1):38 40. by dogs or cats?]. Ned Tijdschr Geneeskd.
1991;135(4):138-140 Corresponding Author:
2. Patil PD, Panchabhai TS, Galwankar SC.
Managing human bites. J Emerg Trauma 9. [Burroughs JR, Soparkar CN, Patrinely Dr Asha Samdani,
Shock. 2009;2(3):186–90. JR, Williams PD, Holck DE. Periocular Consultant,
dog bite injuries and responsible care. Centre for Sight, Hyderabad
3. Simao NR, Borba AM, da Silva AL, Ophthal Plast Reconstr Surg. 2002;
Vieira EM, Carvalhosa AA, Bandeca 18(6):416–9.)
MC, Borges AH. Animal bite injuries to
the face: a case report. J Int Oral Health. 10. https://www.cdc.gov/rabies/medical_
2013;5(4):68–72. care/vaccine.html
4. (https://www.aao.org/eyenet/article/ 11. Rui-feng, C., Li-song, H., Ji-bo, Z. et
dog-bites-in-children-oculoplastic- al. Emergency treatment on facial
urgency-in-er) laceration of dog bite wounds
with immediate primary closure: a
5. Abuabara A. A review of facial injuries prospective randomized trial study.
due to dog bites. Medicina Oral, BMC Emerg Med 13, S2 (2013). https://
Patologia Oral y Cirugia Bucal. 2006 doi.org/10.1186/1471-227X-13-S1-S2
Jul;11(4):E348-50.)
12. Paschos NK, Makris EA, Gantsos A,
6. Stefanopoulos PK, Tarantzopoulou AD. Georgoulis AD. Primary closure versus non-
Facial bite wounds: management update. closure of dog bite wounds. A randomised
60 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times
Subspeciality-Oculoplasty
Recent Updates in the Staging of
Ocular and Orbital Tumors
Toshit Varshney MBBS, Pallavi Singh MD, Rachna Meel MS
Oculoplasty, Tumor & Pediatric Ophthalmology Services,
Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
Abstract: Ocular oncology is a rapidly evolving field with new information coming to light about the clinical and pathologic features of
tumors every few years. This has a significant bearing in terms of the prognosis and treatment of these cancers. As a result, cancer staging
systems are updated frequently to reflect these developments. Our article provides a comprehensive list of the recent updates in staging of
ocular tumors. The latest edition of the American Joint Committee on Cancer (AJCC) classification includes changes in the classification of
tumors of the eyelid, conjunctiva, uvea, lacrimal gland, and ocular adnexa. Staging of retinoblastoma and ocular sarcoma has also been
updated. Updated nomenclature of vascular anomalies (neoplasms and malformations) as defined by the 2018 meeting of the ISSVA
(International Society for Study of Vascular Anomalies) has also been included.
This article aims to review, any Table 1: AJCC-TNM classification of Conjunctival Carcinoma 8th edition
changes in the classification and/or
nomenclature of orbital and ocular T Category Criteria
tumours and vascular malformations in TX Primary tumor cannot be assessed
last few years. Recently the 8th edition of T0 No evidence of primary tumor
AJCC was published. This has brought Tis Carcinoma in situ
changes in tumour grading of the T1 Tumor (≤5 mm in greatest dimension) invades through the
following tumours of eye and orbit.
conjunctival basement membrane without invasion of adjacent
Conjunctival Carcinoma (OSSN) structures
The AJCC-TNM staging, which applies T2 Tumor (>5 mm in greatest dimension) invades through the
predominantly to conjunctival conjunctival basement membrane without invasion of adjacent
intraepithelial neoplasia (CIN), structures
squamous cell carcinoma and other T3 Tumor invades adjacent structures (excluding the orbit)
histologic subtypes, is based on the T4 Tumor invades the orbit with or without further extension
degree of depth of invasion and the size T4a Tumor invades orbital soft tissues without bone invasion
and extent of involvement of adjoining T4b Tumor invades bone
structures. The 8th edition (2016), unlike T4c Tumor invades adjacent paranasal sinuses
the previous classifications, has included T4d Tumor invades brain
histological criteria along with clinical N Category
criteria (Table 1). The term ‘invasion NX Regional lymph nodes cannot be assessed
of conjunctival basement membrane’ N0 No regional lymph node metastasis
has been added in the definitions of T1 N1 Regional lymph node metastasis
and T2, to define the extent of invasion M Category
more precisely1. This necessitates M0 No distant metastasis
the need for a biopsy if the same is M1 Distant metastasis
not clear on clinical examination2. G G Definition
Additional prognostic factors have been GX Grade cannot be assessed
added such as, presence or absence of G1 Well differentiated
subepithelial invasion, as determined G2 Moderately differentiated
by histopathologic examination; G3 Poorly differentiated
tumour size as determined by clinical G4 Undifferentiated
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measurement, clock hour evaluation, Conjunctival Melanoma based on size and location of positive
and UBM (ultrasound biomicroscopy); In the 8th edition of AJCC classification lymph node(s). Stage groups have been
and local invasion as assessed by (Table 3) criteria of T categories have modified to incorporate new T and N
gonioscopy, ultrasound, and radiologic changed to describe circumferential categories; Stage III is defined as node-
testing. extent, criteria of N category have positive disease and Stage IV as distant
changed to describe whether a biopsy metastases. This new classification
Various studies have shown that using was performed. Histologic grade as allow for a more objective and consistent
the AJCC classification majority of described in the TNM classification has designation of the T category6.
cases fall into stage T33,4, an unbalanced been Histopathologic grade: This grade
distribution which can largely be represents the origin of the primary Uveal Melanoma (Choroidal and
attributed to the limbal origin of OSSN tumour. Ciliary Body Melanoma)
and hence an early involvement of the In 7th edition of AJCC classification, the
adjacent cornea. Also, both involvement Eyelid Carcinoma tumor extent was classified in T1-4, on
of ocular coats and an overt intraocular In the 8th edition of AJCC classification the basis of involvement of ciliary body,
extension are grouped into stage T3; (Table 4), the cutoff for T2 tumor was sclera or extrascleral extension only.
whereas the former can be managed shifted from 5 to 10 mm. Tarsal plate
with immunotherapy followed by wide or full-thickness eyelid involvement In the 8th edition of AJCC classification,
surgical excision, the later requires which were earlier classified as T2a the tumor extent (T) is based on largest
enucleation. All these lacunae have and b respectively have been made into basal diameter, with subclassifications
addressed in a new classification subcategories for T1-3. N1 category on the basis of ciliary body and
scheme proposed for OSSN (Table2)5. has been divided into N1 and N2 extraocular involvement. The N1 has
been subcategorized such that N1a is for
Table 2: Proposal for the new classification for Conjunctival carcinoma
Group/ Limbal Maximal Imaging findings Treatment Risk with upfront
grade involvement basal diameter recommended surgical excision
(clock (mm) Minimal risk of side
hours) effects
Moderate risk of
Grade I: OSSN with no invasion into ocular coats clinically/on imaging (UBM) side effects (limbal
stem cell deficiency,
A (small) ≤3 ≤5 No invasion into ocular Surgical excision with symblepharon
coats/globe on UBM edge control formation)
High risk of side effects,
B (large) >3 to <6 5–15 No invasion into ocular Immunotherapy/ high risk of recurrence
coats/globe on UBM immunoreduction f/b
—
surgical excision —
C (diffuse) ≥6 ≥15 No invasion into ocular Immunoreduction with
coats/globe on UBM interferons f/b surgical
excision
Grade II: OSSN with invasion into ocular coats (sclera/corneal stroma) on imaging
Any Any Scleral or corneal Excision with
stromal invasion on lamellar sclerectomy
UBM or keratectomy
+ cryotherapy of
margins
Grade III: OSSN with intraocular invasion
Any Any Intraocular Enucleation
involvement present
(clinically/UBM)
Grade IV: OSSN with intraorbital extension
Any Any Orbital extension on Exenteration
CT/MRI
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Table 3: AJCC-TNM classification of Conjunctival Melanoma 8th edition
Clinical tumor (cT) cT Criteria
Category
T1 Tumor of the bulbar conjunctiva
1a. <1 quadrant; 1b. ≥1 to <2 quadrants; 1c. ≥2 to <3 quadrants; 1d. ≥3 quadrants
T2 Tumor of the nonbulbar (forniceal, palpebral, tarsal) conjunctiva, and tumor involving the caruncle
2a. Noncaruncular, and ≤1 quadrant of the nonbulbar conjunctiva involved
2b. Noncaruncular, and >1 quadrant of the nonbulbar conjunctiva involved
2c. Caruncular, and ≤1 quadrant of the nonbulbar conjunctiva involved
2d. Caruncular, and >1 quadrant of the nonbulbar conjunctiva involved
T3 Tumor of any size with local invasion
3a Globe; 3b Eyelid; 3c Orbit; 3d Nasolacrimal duct and/or lacrimal sac and/or paranasal sinuses
T4 Tumor of any size with invasion of the central nervous system
Pathological tumor pT Criteria
(pT) Category
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Melanoma confined to the conjunctivalepithelium
T1 Tumor of the bulbar conjunctiva
1a Tumor of the bulbar conjunctiva with invasion of the substantia propria, not more than 2.0 mm
in thickness
1b Tumor of the bulbar conjunctiva with invasion of the substantia propria, more than 2.0 mm in
thickness
T2 Tumor of the nonbulbar (forniceal, palpebral, tarsal) conjunctiva, and tumor involving the caruncle
2a Tumor of the nonbulbar conjunctiva with invasion of the substantia propria, not more than 2.0
mm in thickness
2b Tumor of the nonbulbar conjunctiva with invasion of the substantia propria, more than 2.0 mm
in thickness
T3 Tumor of any size with local invasion
3a Globe; 3b Eyelid; 3c Orbit; 3d Nasolacrimal duct and/or lacrimal sac and/or paranasal sinuses
T4 Tumor of any size with invasion of the central nervous system
N Category N Criteria
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
M Category M Criteria
M0 No distant metastasis
M1 Distant metastasis
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Table 4: AJCC-TNM classification of Eyelid Carcinoma 8th edition
T Category T Criteria
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor ≤10 mm in greatest dimension
1a Tumor does not invade the tarsal plate or eyelid margin
1b Tumor invades the tarsal plate or eyelid margin
1c Tumor involves full thickness of the eyelid
T2 Tumor >10 mm but ≤20 mm in greatest dimension
2a Tumor does not invade the tarsal plate or eyelid margin
2b Tumor invades the tarsal plate or eyelid margin
2c Tumor involves full thickness of the eyelid
T3 Tumor >20 mm but ≤30 mm in greatest dimension
3a Tumor does not invade the tarsal plate or eyelid margin
3b Tumor invades the tarsal plate or eyelid margin
3c Tumor involves full thickness of the eyelid
T4 Any eyelid tumor that invades adjacent ocular, orbital, or facial structures
4a Tumor invades ocular or intraorbital structures
4b Tumor invades (or erodes through) the bony walls of the orbit or extends to the paranasal sinuses or
invades the lacrimal sac/ nasolacrimal duct or brain
N Category N Criteria
NX Regional lymph nodes cannot be assessed
N0 No evidence of lymph node involvement
N1 Metastasis in a single ipsilateral regional lymph node, ≤3 cm in greatest dimension
1a Metastasis in a single ipsilateral lymph node based on clinical evaluation or imaging findings
1b Metastasis in a single ipsilateral lymph node based on lymph node biopsy
N2 Metastasis in a single ipsilateral lymph node, >3 cm in greatest dimension, or in bilateral or contralateral
lymph nodes
2a Metastasis documented based on clinical evaluation or imaging findings
2b Metastasis documented based on microscopic findings on lymph node biopsy
M Category M Criteria
M0 No distant metastasis
M1 Distant metastasis
nodal metastasis and N1b is for discrete Figure 1 Classification of ciliary body and choroid uveal melanoma based on thickness and
tumor deposits in the orbit which diameter
is not contiguous with the primary
tumor.7 The T, N and M are combined
into prognostic stages (1 to 4), with an
increase in staging indicating a higher
risk of metastasis and mortality.
Also post enucleation, if done as a part
of management, a histologic grading (G)
should be assessed. As of now, they have
not defined its prognostic role but may
be incorporated in the future.1
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Table 5: AJCC-TNM classification of Choroidal and Ciliary Body Melanomas 8th edition
T Category T Criteria
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor size category 1
1a Tumor size category 1 without ciliary body involvement and extraocular extension
1b Tumor size category 1 with ciliary body involvement
1c Tumor size category 1 without ciliary body involvement but with extraocular extension ≤5 mm in largest
diameter
1d Tumor size category 1 with ciliary body involvement and extraocular extension ≤5 mm in largest diameter
T2 Tumor size category 2
2a Tumor size category 2 without ciliary body involvement and extraocular extension
2b Tumor size category 2 with ciliary body involvement
2c Tumor size category 2 without ciliary body involvement but with extraocular extension ≤5 mm in largest
diameter
2d Tumor size category 2 with ciliary body involvement and extraocular extension ≤5 mm in largest diameter
T3 Tumor size category 3
3a Tumor size category 3 without ciliary body involvement and extraocular extension
3b Tumor size category 3 with ciliary body involvement
3c Tumor size category 3 without ciliary body involvement but with extraocular extension ≤5 mm in largest
diameter
3d Tumor size category 3 with ciliary body involvement and extraocular extension ≤5 mm in largest diameter
T4 Tumor size category 4
4a Tumor size category 4 without ciliary body involvement and extraocular extension
4b Tumor size category 4 with ciliary body involvement
4c Tumor size category 4 without ciliary body involvement but with extraocular extension ≤5 mm in largest
diameter
4d Tumor size category 4 with ciliary body involvement and extraocular extension ≤5 mm in largest diameter
4eAny tumor size category with extraocular extension >5 mm in largest diameter
N Category N Criteria
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node involvement
N1 Regional lymph node metastases or discrete tumor deposits in the orbit
1a Metastasis in one or more regional lymph node(s)
1b No regional lymph nodes are positive, but there are discrete tumor deposits in the orbit that are no
contiguous to the eye (choroidal and ciliary body).
M Category M Criteria
M0 No distant metastasis
M1 Distant metastasis
1a Largest diameter of the largest metastasis ≤3.0 cm
1b Largest diameter of the largest metastasis 3.1–8.0 cm
1c Largest diameter of the largest metastasis ≥8.1 cm
Note: Primary ciliary body and choroidal melanomas are classified according to the four tumor size categories defined in (Figure 1)
Primary Iris Melanoma been expanded to include invasion of to the involvement of the ciliary
Iris melanoma is classified separately the ciliary body only (T2a), ciliary body body, choroid, or both, with a scleral
from posterior melanoma of the ciliary and choroid (T2b) and involvement extension (T3). Subcategory T3a (scleral
body and choroid in the 8th edition of either or both of this structures extension and secondary glaucoma) has
of AJCC classification . Compared to along with secondary glaucoma (T2c). been completely removed due to the
previous editions, category T2, has Category T3 has been condensed rarity of T3 tumors8.
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Table 6. AJCC-TNM classification of Iris Melanomas 8th edition
T Category T Criteria
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor limited to the iris
1a Tumor limited to the iris, not more than 3 clock hours in size
1b Tumor limited to the iris, more than 3 clock hours insize
1c Tumor limited to the iris with secondary glaucoma
T2 Tumor confluent with or extending into the ciliary body, choroid, or both
2a Tumor confluent with or extending into the ciliary body, without secondary glaucoma
2b Tumor confluent with or extending into the ciliary body and choroid, without secondary glaucoma
2c Tumor confluent with or extending into the ciliary body, choroid, or both, with secondary glaucoma
T3 Tumor confluent with or extending into the ciliary body, choroid, or both, with scleral extension
T4 Tumor with extrascleral extension
4a Tumor with extrascleral extension ≤5 mm in largest diameter
4b Tumor with extrascleral extension >5 mm in largest diameter
N Category N Criteria
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node involvement
N1 Regional lymph node metastases or discrete tumor deposits in the orbit
1a Metastasis in one or more regional lymph node(s)
1b No regional lymph nodes are positive, but there are discrete tumor deposits in the orbit that are no
contiguous to the eye (choroidal and ciliary body)
M Category M Criteria
M0 No distant metastasis
M1 Distant metastasis
1a Largest diameter of the largest metastasis ≤3.0 cm
1b Largest diameter of the largest metastasis 3.1–8.0 cm
1c Largest diameter of the largest metastasis ≥8.1 cm
Retinoblastoma Just to give a comparison between both involvement of periosteum and
ICRB and AJCC classification, patients bone respectively.T4 is for extra-orbital
The International Intraocular with Group A and B will come under involvement with further subdivisions
Retinoblastoma Classification (IIRC) cT1a and cT1b respectively, those with into a (< 2cm), b (>2cm and <4cm) and c
(2005) was introduced to predict eye Group C and D will be categorized (>4cm) based on size.
salvage and high-risk disease. With under cT2 and group E will fall under
a modification, the International cT3. The AJCC TNM scheme also has a Ocular Adnexal Lymphoma
Classification of Retinoblastoma (ICRB) pathological (pTNM) sub-classification
was published in 2006. An Extraocular for ophthalmic pathologists9 (Table In the 8th edition of AJCC classification
Retinoblastoma Staging System was 5,6). (Table 8), T categories have been
proposed in the same year. The 8th revised and are now based on anatomic
edition of AJCC (2016) classification has Lacrimal Gland Carcinoma extent (conjunctival involvement,
a cTNMH scheme where c for clinical In the 8th edition of AJCC Classification orbital involvement, pre-septal
and a hereditary (H) component have (Table 7), the T system has been eyelid involvement and extra-orbital
been newly incorporated . The primary modified, with T1-3 based on size (as involvement) of disease instead of
tumor in cT is classified as intraretinal before) and a further subdivision into tumor size. Subcategories have been
(cT1), intraocular (cT2), advanced a, b and c to define no involvement (a); removed. N categories have been revised
intraocular (cT3) or extraocular (cT4). periosteal involvement only (b); and to reflect site of nodal involvement.
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Table 7. A comparison between ICRB and Clinical cT of 8th edition AJCC-TNM classification of Retinoblastoma
International Classification of Retinoblastoma (ICRB) 2006: AJCC 8th ed
Group Description Grouping System Category Criteria
(Risk of losing the eye is deter-
mined by extent of intraocular
tumor dissemination)
cT1 Intra-retinal tumor(s) with
subretinal fluid ≤5mm from
base of any tumor
A Very low risk: Tumor ≤3 mm in basal dimension or cT1a Tumor size < 3mm and
Eyes with small discrete tumors thickness >1.5mm(1DD) away from
disc or macula
away from critical structures.
(Small round tumor(s) located
away from the fovea and disc)
B Low risk: Tumor >3 mm in basal dimension or cT1b Tumor size > 3mm or
Eyes with discrete retinal tumor thickness, <1.5mm away from disc or
of any size or location without OR any of the following: fovea
vitreous or subretinal seeding • Macular location ≤3 mm to foveola
(All eyes without tumor dissemi- • Juxta-papillary location ≤1.5 mm to disc
nation not in • Clear subretinal fluid ≤3 mm from
Group A) margin
cT2 Intraocular tumor(s) with
RD or Seeding (vitreous or
subretinal)
C Moderate risk: One of the following: cT2a Subretinal fluid >5 mm from
the base of any tumor
Eyes with discrete retinal tumors • Subretinal seeds ≤3 mm from tumor cT2b Vitreous seeding and/or
of any size and location with • Vitreous seeds ≤3 mm from tumor
only focal vitreous or subretinal • Both subretinal and vitreous seeds ≤3 subretinal seeding
seeding mm from tumor
• Less than one quadrant of subretinal
fluid in the fundus
D High risk: One of the following:
Eyes with massive nondiscrete • Subretinal seeds >3 mm from tumor
tumors and/or diffuse vitreous or • Vitreous seeds >3 mm from tumor
subretinal seeding • Both subretinal and vitreous seeds >3
mm from tumor
• Greater than one quadrant of subretinal
fluid in the fundus
E Very high risk: Extensive retinoblastoma or one of the cT3 Advanced intraocular tu-
Eyes that have been destroyed following: cT3a mor(s)
anatomically or functionally by • Phthisis bulbi or orbital cellulitis cT3b
• Invasion of postlaminar optic nerve, Phthisis or pre-phthisis bul-
bi
the tumor choroid (>2 mm), sclera, orbit, anterior
Tumor invasion of choroid,
chamber cT3c pars plana, ciliary body, lens,
• Tumor anterior to the anterior vitreous cT3d
face, including the ciliary body or iris zonules, iris, or anterior
chamber
• Neovascular glaucoma cT3e Raised intraocular pressure
• Opaque media from hemorrhage in with Neovascularization
anterior chamber, vitreous, or subret-
inal space and/or buphthalmos
Hyphema and/or massive
• Diffuse infiltrating tumor vitreous hemorrhage
Aseptic orbital cellulitis
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cT4 Extraocular tumor(s) involv-
CT4a ing orbit, including optic
nerve
Ct4b Radiologic evidence of ret-
robulbar optic nerve involve-
ment or thickening of optic
nerve or involvement of
orbital tissues
Extraocular tumor clinically
evident with proptosis and/or
an orbital mass
Table 8: Definition of Heritable Trait (H) in AJCC 8th edition TNM classification of retinoblastoma
H Category H Criteria
HX Unknown or insufficient evidence of a constitutional RB1 gene mutation
H0 Normal RB1 alleles in blood tested with demonstrated high-sensitivity assays
H1 Bilateral retinoblastoma, retinoblastoma with an intracranial primitive neuroectodermal tumor (i.e.,
trilateral retinoblastoma), patient with family history of retinoblastoma, or molecular definition of a
constitutional RB1 gene mutation
Table 9: AJCC-TNM classification of Lacrimal Carcinoma 8th edition
T Category T Criteria
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor ≤2 cm in greatest dimension with or without extraglandular extension into the orbital soft tissue
1a No periosteal or bone involvement
1b Periosteal involvement only
1c Periosteal and bone involvement
T2 Tumor >2 cm and ≤4 cm in greatest dimension
2a No periosteal or bone involvement
2b Periosteal involvement only
2c Periosteal and bone involvement
T3 Tumor >4 cm in greatest dimension
3a No periosteal or bone involvement
3b Periosteal involvement only
3c Periosteal and bone involvement
T4 Involvement of adjacent structures, including sinuses, temporal fossa, pterygoid fossa, superior orbital
fissure, cavernous sinus, or brain
4a Tumor ≤2 cm in greatest dimension
4b Tumor >2 cm and ≤4 cm in greatest dimension
4c Tumor >4 cm in greatest dimension
N Category N Criteria
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
M Category M Criteria
M0 No distant metastasis
M1 Distant metastasis
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Table 10: AJCC-TNM classification of Ocular Adenexal Lymphoma 8th edition
T Category T Criteria
TX Lymphoma extent not specified
T0 No evidence of lymphoma
T1 Lymphoma involving the conjunctiva alone without eyelid or orbital involvement
T2 Lymphoma with orbital involvement with or without conjunctival involvement
T3 Lymphoma with preseptal eyelid involvement with or without orbital involvement and with or without
conjunctival involvement
T4 Orbital adnexal lymphoma and extraorbital lymphoma extending beyond the orbit to adjacent structures,
such as bone, maxillofacial sinuses, and brain.
N Category N Criteria
NX Involvement of lymph nodes not assessed
N0 No evidence of lymph node involvement
N1 Involvement of lymph node region or regions draining the ocular adnexal structures and superior to the
mediastinum (preauricular, parotid, submandibular, and cervical nodes)
N1a Involvement of a single lymph node region superior to the mediastinum
N1b Involvement of two or more lymph node regions, superior to the mediastinum
N2 Involvement of lymph node regions of the mediastinum
N3 Diffuse or disseminated involvement of peripheral and central lymph node regions
M Category M Criteria
M0 No evidence of involvement of other extranodal sites
M1 Evidence of involvement of other extranodal sites
M1a Noncontiguous involvement of tissues or organs external to the ocular adnexa (e.g., parotid glands,
submandibular gland, lung, liver, spleen, kidney, breast)
M1b Lymphomatous involvement of the bone marrow
M1c Both M1a and M1b involvement
Table 11: ISSVA classification for vascular anomalies
Vascular tumors Vascular malformations
Simple Combined° Anomalies of Associated with other
major named anomalies
Benign Capillary malformations CVM vessels • Klippel-Trenaunay
• Infantile hemangioma / • Nevus simplex / salmon patch CLM syndrome
Hemangioma of infancy • Cutaneous and/or mucosal CM LVM Affect • Sturge-Weber
• Congenital hemangioma (port-wine” stain) CVLM -lymphatics syndrome
• Pyogenic granuloma • Others CAVM -veins • Others
• Others CLAVM -arteries
Locally aggressive or Others
borderline
• Kaposi Sarcoma Lymphatic malformations
• Others • Common (cystic)
-Macrocystic LM
Malignant -Microcystic LM
• Angiosarcoma -Mixed cystic LM
• Others • Generalized lymphatic anomaly
(GLA)
-Kaposiform lymphangiomatosis
(KLA)
• Others
Venous malformations
-Cavernous haemangioma
Arteriovenous malformations
Arteriovenous fistula
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Orbital Sarcoma 2. Honavar S. Ocular surface squamous Accessed September 5, 2020. https://
The 8th edition of the AJCC has changed neoplasia: Are we calling a spade a spade? retinatoday.com/articles/2017-july-aug/
the cut-off between T1 and T2 categories Indian J Ophthalmol. 2017;65(10):907. updated-classification-for-primary-iris-
from 15mm to 20 mm. doi:10.4103/ijo.IJO_971_17 melanoma
9. Fabian ID, Reddy A, Sagoo MS.
3. Shields CL, Kaliki S, Kim HJ, et al. Classification and staging of
Interferon for Ocular Surface Squamous retinoblastoma. Community Eye Health.
Vascular tumors and 2018;31(101):11-13.
malformations - Changes in Neoplasia in 81 Cases: Outcomes Based 10. Classification | International Society
Nomenclature for the Study of Vascular Anomalies.
on the American Joint Committee Accessed September 6, 2020. https://
on Cancer Classification. Cornea. www.issva.org/classification
The 2013 World Health Organization 2013;32(3):248–256. doi:10.1097/ 11. Wildgruber M, Sadick M, Müller-Wille
(WHO) classification of vascular soft R, Wohlgemuth WA. Vascular tumors
tissue tumors was based on outdated ICO.0b013e3182523f61 in infants and adolescents. Insights
Imaging. 2019;10(1):1-14. doi:10.1186/
pathological terminology, such as 4. Meel R, Dhiman R, Vanathi M, Pushker N, s13244-019-0718-6
12. http://www.issva.org/UserFiles/file/
‘cavernous’ and ‘capillary’ hemangioma. Tandon R, Devi S. Clinicodemographic ISSVA-Classification-2018.pdf
profile and treatment outcome in
It also did not differentiate between patients of ocular surface squamous Corresponding Author:
vascular tumors and vascular
malformations, a necessary requisite neoplasia. Indian Journal of Dr Toshit Varshney MBBS
Ophthalmology. 2017;65(10):936. Dr. R. P. Centre for Ophthalmic Sciences,
doi:10.4103/ijo.IJO_251_17 All India Institute of Medical Sciences,
for appropriate therapy. In contrast, the New Delhi, India
ISSVA (International Society for Study of
Vascular Anomalies) 2018classification 5. Meel R, Dhiman R. Proposal for
a new classification for ocular
year (Table 11) is clinical-biological surface squamous neoplasia. Eye.
2018;32(7):1284-1285. doi:10.1038/
based and differentiates vascular s41433-018-0058-7
lesions into vascular tumors (true
proliferative neoplasms) and
vascular malformations(defects in 6. Ding S, Sagiv O, Thakar SD, Esmaeli B.
morphogenesis)10,11. The most recent Change in Eyelid Carcinoma T Category
update of this classification in 2018 With Use of the 8th Versus 7th Edition
includes more lesions and reflects a of the American Joint Committee on
more comprehensive understanding of Cancer: Cancer Staging Manual. Ophthal
Plast Reconstr Surg. 2019;35(1):4.
underlying genetic causes12. 7. http://fyra.io. Updated AJCC
Classification for Posterior Uveal
Melanoma. Retina Today. Accessed
References September 5, 2020. https://retinatoday.
1. Amin MB, Edge S, Greene F, et al., com/articles/2018-may-june/updated-
ajcc-classification-for-posterior-uveal-
eds. AJCC Cancer Staging Manual. melanoma
8th ed. Springer International
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2, 2020. https://www.springer.com/gp/ Primary Iris Melanoma. Retina Today.
book/9783319406176
70 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times
Subspeciality-Oculoplasty
Classification Systems in Thyroid
Ophthalmopathy
Karthika Bhaskaran MD, Rachna Meel MS, Deepsekhar Das MD
Oculoplasty, Tumor & Pediatric Ophthalmology Services,
Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
Abstract: Numerous classification systems have been devised for assessing the activity and severity, monitoring progress, and formulating
management plans for thyroid associated ophthalmopathy. The VISA, EUGOGO and CAS scoring systems are commonly used, and have
been discussed in detail in this article.
Thyroid ophthalmopathy is a self- Figure 1: Active thyroid eye disease with bilateral eyelid erythema and edema, diffuse
limiting auto immune process of conjunctival congestion and caruncular edema.
varying severity, associated mainly
with hyperthyroidism but may also TED not responding to medical for three more signs (Table 2), with one
affect euthyroid and hypothyroid management6. point for each, with a maximum score
patients. It affects approximately 25- Mourits et al described the Clinical of 10. A score of 4 or more is suggestive
50% of patients with Grave’s disease. Activity Score (CAS) in 19897 based of active disease at follow up.
Sight-threatening thyroid eye disease on the classic signs of inflammation, Non-specific signs like eyelid swelling,
(TED) occurs in 3-5%1. TED is the and it was modified in 1997 by the erythema and conjunctival congestion
most common cause of unilateral and European Group of Graves’ Orbitopathy should be scored only after other causes
bilateral proptosis in adults. It is a (EUGOGO), (Table 1). of the same are ruled out. When both
biphasic disease with an initial active At the initial visit, patient is given eyelids are affected differently, scoring
phase and a subsequent quiescent a score from 1-7, one point for each is based on the more severely affected
phase. symptom/sign given in Table 1. A score lid. Conjunctival congestion is assessed
of 3 or more indicates active disease without slit-lamp at 1 metre distance. It
Disease stratification (Figure 1). should be diffuse, involving at least one
Management of TED differs according On follow-up visits, patients are assessed quadrant. Chemosis is said to be present
to the activity (active or inactive) and when conjunctiva is separate from the
severity of disease (mild, moderate, sclera for more than one-third of the
severe). Hence, assessing these
clinically is critical for therapeutic
decision-making in TED. Various
classification systems have been
described for scoring of clinical
features in TED, like NOSPECS2, VISA3,
EUGOGO4 and CAS5.
Assessment of Clinical Activity
Differentiating active disease from
quiescent TED is important because
active or inflammatory TED is
mainly managed medically with
immunosuppressants, while surgical
intervention is reserved for inactive
disease to improve function and
cosmesis, and in some cases of active
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Subspeciality-Oculoplasty
Table 1: Clinical Activity Score 1. The NOSPECS classification (No
Pain Pain, oppressive feeling on or behind the globe, over the last 4 physical signs or symptoms, Only
signs, Soft tissue involvement,
weeks Proptosis, Extraocular muscle
Pain on attempted up, down or side gaze during the last 4 weeks signs, Corneal involvement,
Redness Redness of the eyelid(s) and Sight loss) was reported by
Diffuse redness of the conjunctiva, covering at least one quadrant Werner2 in 1969 and modified
Swelling Swelling of the eyelid(s) thereafter10. Since it exclusively
Chemosis indicates the clinical severity of
Swelling of the caruncle the disease without differentiating
the inflammatory symptomatic
Table 2: Clinical Activity Score (contd) stage from the non-inflammatory
Increase of 2 mm or more in proptosis over the last 1-3 months stationary stage, or assessing rate of
Decrease in uniocular motility in any direction of 18 degrees progression of the disease, its use in
Decrease in visual acuity equivalent to 1 Snellen line clinical practice is limited.
Diffuse redness of the conjunctiva, covering at least one quadrant
Swelling of the eyelid(s) 2. EUGOGO has classified severity
Chemosis of TED as mild, moderate-severe
Swelling of the caruncle or sight-threatening disease. Some
severity parameters, especially
Figure 2: Moderate – severe thyroid ophthalmopathy with severe lid retraction soft tissue signs are evaluated by
comparison with an image atlas
palpebral height, or when conjunctiva take into account the diurnal variation developed by the group8.
prolapses anterior to the grey-line of the of symptoms.
lid. Caruncular involvement is present Mild: The patient’s QOL is minimally
when it is inflamed or plica prolapses Assessment of Severity affected. They may have one or more of
through closed eyelids. It is the physical sequelae of disease the following signs:
activity, and includes lid retraction,
While CAS is easy to use in routine proptosis, extraocular muscle yy Lid retraction < 2mm
clinical practice, it has a few thickening and restriction, strabismus, yy Mild soft tissue involvement
disadvantages. Although very specific, diplopia, expansion of orbital fat, yy Proptosis < 3 mm
CAS is not very sensitive.5 For instance, compressive optic neuropathy, ocular yy Transient or no diplopia
some patients with DON may be missed surface disease9, and the impact of the yy Exposure keratopathy responding to
when they present with low CAS scores.8 disease on the patient’s quality of life
Hence, CAS should be combined with (QOL). Three classification systems lubricants.
other parameters of disease activity, like assess severity of TED. Moderate-Severe: QOL is affected
laboratory evaluation.5 Also, it does not enough to warrant treatment
(immunosuppression for active disease
and surgical management for inactive
disease). Risk for loss of visual acuity is
low. They may have at least one of the
following signs (Figure 2).
yy Lid retraction > 2mm
yy Moderate/severe soft tissue
involvement
yy Proptosis > 3 mm
yy Intermittent or constant diplopia.
Sight-threatening disease: This category
requires immediate intervention and
includes patients with
yy Dysthyroid optic neuropathy (Figure
3).
yy Exposure keratopathy (Figure 4).
72 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times
Subspeciality-Oculoplasty
Figure 3: Computed Tomography of orbit (axial and coronal sections) showing bulky Mourits. Acute inflammatory
extraocular muscles, apical crowding, and optic nerve compression signs like conjunctival, caruncular
and lid edema (upper, lower lids
Figure 4: Sight-threatening thyroid eye disease with exposure keratopathy scored separately), lid erythema,
conjunctival congestion and
yy Globe luxation/Choroidal folds. The VISA classification (Figure 5) was retrobulbar pain are assessed.
Evaluation of soft tissue inflammation is proposed by Dolman and Rootman Chemosis is graded 1 or 2 depending
similar to CAS but pain is not taken into (2006) and adopted by the International on whether the conjunctiva lies
account. Eyelid swelling is classified as Thyroid Eye Disease Society. It consists posterior or anterior to the grey line
mild, moderate(subcutaneous fluid/ of subjective and objective evaluation of the lid, respectively. Eyelid edema
skin thickening), and severe (tense of 4 disease endpoints which are scored, is graded 1 if there is no overhanging
subcutaneous fluid or thickened skin the maximum score being 20. It also tissue and 2 when it causes rolls
with lower eyelid festoons or upper lid gives an idea about progression of the in eyelid skin including festoons
fold remains rounded on downgaze). disease by labelling each parameter as in lower eyelid skin. The presence
Conjunctival congestion may be mild, better (b), same (s) or worse (w) since last of diurnal changes of these signs
moderate(definite redness of < 50% visit. The sequence of the parameters contributes an additional point to
bulbar conjunctiva except plica and (V-I-S-A) indicate the priority for the score. Patients with score of 4
caruncle) or severe (definite redness of management. or less are managed conservatively.
150%). Those with higher score require
yy -Vision (score:0-1): Visual functions intervention.
While this is a very practical are assessed, including best-corrected yy Strabismus (Diplopia score: 0-3,
classification for management of the visual acuity, pupillary reaction and Ocular motility restriction score:0-3).
disease, it does not differentiate between optic nerve function tests. A score Diplopia is scored based on its
moderate and severe forms of the of 1 is given if optic neuropathy is presence during one gaze only (1
disease. Also, ocular motility restriction present. point), intermittent (2 points), or
is not included in assessment of disease constant diplopia (3 points). Amount
severity8. yy -Inflammation (score:0-10): The of ocular motility is scored from 0-3
inflammatory score is a derivative for ranges of duction >45 °, 30-45 °, 15-
of the CAS system developed by 30° and <15° respectively. A change
of 12° or more in any direction is
considered a sign of progressive
disease.
yy Appearance (score:0-3) Proptosis,
lid retraction, scleral show, levator
function and lagophthalmos are
measured. Fat pockets, ocular
surface disorders (grittiness, dryness,
photophobia) and corneal status are
also assessed.
To conclude, both activity and severity
of TED should be known for optimal
management of the disease. VISA
and EUGOGO systems not only give
diagnostic classifications, but also
guide the clinician in the management
of TED. However, they are not inter-
changeable, and patients should not
be evaluated using different grading
systems on subsequent visits.
References
1. Marcocci C, Bartalena L, Bogazzi F,
Panicucci M, Pinchera A. Studies on
the occurrence of ophthalmopathy in
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Figure 5: VISA classification system www.dosonline.org/dos-times
74 DOS Times - Volume 26, Number 2, September-October 2020
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Graves’ disease. Acta Endocrinol. 1989 6. Sahlı E, Gündüz K. Thyroid-associated North America. 2005 Oct;38(5):1043–74.
Apr;120(4):473–8. Ophthalmopathy. Turk J Ophthalmol. 10. Werner SC. Modification of the
2017 Apr;47(2):94–105.
2. Werner SC. Classification of the eye Classification of the Eye Changes of
changes of Grave’s disease. J Clin 7. Mourits MP, Koornneef L, Wiersinga Graves’ Disease. American Journal of
Endocrinol Metab. 1969 Jul;29(7):982–4. WM, Prummel MF, Berghout A, van Ophthalmology. 1977 May;83(5):725–7.
der Gaag R. Clinical criteria for the
3. Dolman PJ, Rootman J. VISA assessment of disease activity in Graves’ Corresponding Author:
Classification for Graves orbitopathy. ophthalmopathy: a novel approach.
Ophthalmic Plast Reconstr Surg. 2006 British Journal of Ophthalmology. 1989 Dr. Karthika Bhaskaran MD
Oct;22(5):319–24. Aug 1;73(8):639–44. Oculoplasty, Tumor & Pediatric
Ophthalmology Services,
4. Bartalena L, Baldeschi L, Dickinson AJ, 8. Barrio-Barrio J, Sabater AL, Bonet-Farriol Dr. R. P. Centre for Ophthalmic Sciences,
Eckstein A, Kendall-Taylor P, Marcocci E, Velázquez-Villoria Á, Galofré JC. All India Institute of Medical Sciences,
C, et al. Consensus statement of the Graves’ Ophthalmopathy: VISA versus New Delhi, India
European group on Graves’ orbitopathy EUGOGO Classification, Assessment,
(EUGOGO) on management of and Management. J Ophthalmol
Graves’ orbitopathy. Thyroid. 2008 [Internet]. 2015 [cited 2020 Apr 12];2015.
Mar;18(3):333–46. Available from: https://www.ncbi.nlm.
nih.gov/pmc/articles/PMC4553342.
5. Mourits MP, Prummel MF, Wiersinga
WM, Koornneef L. Clinical activity score 9. Rose JG, Burkat CN, Boxrud CA.
as a guide in the management of patients Diagnosis and Management of Thyroid
with Graves’ ophthalmopathy. Clin Orbitopathy. Otolaryngologic Clinics of
Endocrinol (Oxf). 1997 Jul;47(1):9–14.
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Subspeciality-Oculoplasty
Pathology of Intraocular Tumours
Lata Singh1, Mithalesh Kumar Singh2, Seema Kashyap3 MD
1. Department of Pediatrics, All India Institute of Medical Sciences, Delhi, India
2. Department of Dermatology, University of Wisconsin, Madison, USA.
3. Department of Ocular Pathology, Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, Delhi, India
Keywords: Retinoblastoma, Uveal Melanoma, Pathology, Biomarkers.
Abstract: The most common intraocular tumor in children and adults are retinoblastoma and uveal melanoma, respectively. Retinoblastoma
is caused by mutational inactivation of both alleles of the RB1gene which encodes Rb protein that acts as a tumor suppressor, whereas uveal
melanoma develops from uvealmelanocytes that are derived from the neural crest. The treatment for uveal melanoma has not changed much
over the years, unlike retinoblastoma, in which advancements over the last few decades have resulted in significant increase in survival.
Predictors of metastasis or recurrence are histopathological high-risk factors in retinoblastoma. Prognostication of uveal melanoma depends
on tumour size, location, histopathological staging, cytogenetic abnormalities, and molecular profiling. This review article highlights the
pathology, genetics, molecular pathology and biomarkersfor diagnostic and prognostic purposes for these tumors.
Retinoblastoma sporadic in newly diagnosed cases of Tumor differentiation is categorized
Retinoblastoma (Rb) is the most retinoblastoma6. All cases of bilateral into well differentiated (>50% rosettes,
common intraocular malignancy of retinoblastoma involve germinal either Homer-Wright or Flexner-
childhood and infancy accounting mutations. Almost 15% of unilateral Wintersteiner) or poorly differentiated
for 3% of all pediatrics cancers1. sporadic retinoblastoma are caused retinoblastoma (<50% rosettes).
The incidence of retinoblastoma is by germinal mutations affecting Prognosis in patients with poorly
approximately one case per 15,000– only one eye while the 85% are differentiated retinoblastoma is poorer
20,000 live birthsworldwide, which sporadic. Knudson proposed thetwo- as compared towell differentiated
corresponds to about 9000 new cases hit hypothesis where he described retinoblastoma9. Tumor necrosis is
every year2. There is no racial or the occurrence of two consecutive graded as none (<25%), moderate (25%-
gender predisposition. The survival of mutations for the conversion of a 50 percent), or extensive (>50 percent).
retinoblastoma is 95-98% in developed normalretinal cell into a malignant Choroidal involvement is divided into
countries3. cell7. It is caused by inactivation focal invasion (tumor focus of less
of both alleles of RB1 gene, tumor than 3 mm in any diameter) or massive
Clinically, retinoblastoma present suppressor gene. Gallie et al., showed invasion (focus of tumor measuring
as leukocoria, strabismus, painful that few of Rb case sexhibit MYCN 3mm or more in any diameter) as per
blind eye and loss of vision4. With gene amplification without RB1 gene the Retinoblastoma Staging Working
the advancement in treatment and mutation and these behave in an Group10. Optic nerve involvement
multidisciplinary approach, eye aggressive manner8. is categorized as prelaminar, optic
salvage is possible in group A through nerve head, postlaminar, and resected
D intraocular tumors. However, in Histopathology of Retinoblastoma margin invasion11. Identification of
group E tumors and group D (unilateral An enucleated eyeball with Rb reveals histopathological high-risk factors is
cases), enucleation always remains the a grey white tumor with encephaloid useful in the management of high-
choice of treatment5. Higher incidences or brain-like appearance along with risk retinoblastoma patients and
of histopathological high-risk factors chalky areas of calcification and considering adjuvant chemotherapyis
in enucleated eyes from developing yellow necrotic areas. On microscopic given to these patients12.
countries are seen as opposed to examination, Rb reveals a tumor
developed countries. composed of small hyperchromatic AJCC classification
cells with a high nuclear to cytoplasmic
Genetics ratio with large areas of necrosis and Germline predisposition in
Only 6% are familial while 94% are multifocal area of calcifications. retinoblastomahas been incorporated
as stage category “H” into the 8th
76 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times
Subspeciality-Oculoplasty
edition of American Joint Committee common primary intraocular by standard karyotyping. They have
on Cancer (AJCC) as TNMH (tumor, malignancy that develops from uveal subsequently been confirmed with
node, metastasis, heritable trait) clinical melanocytes18. Melanomas, commonly other techniques such as fluorescence in
and pathological staging system which arise in the choroid followed by ciliary situ hybridization (FISH), comparative
is known to be the first evidence-based body and iris. Incidence of UM in North genomic hybridization (CGH), spectral
system for predicting overall prognosis America and Europe is reported in karyotyping, microsatellite analysis
of both eye(s) and patients13. 2–8 million persons19. High mortality (MSA), multiplex ligation-dependent
rate is found in UM because of distant probe amplification (MLPA), and
Molecular biomarkers metastasis, and approximately 50% single nucleotide polymorphism
of the lesions metastasize within 15 (SNP) analysis. Chromosome 3 loss is
Recent studies recognized the role of years20. While advancements in UM associated with a reduction in 5-year
various molecular biomarkers and treatment have resulted in improved survival to approximately 50%24.
therapeutic target in the pathogenesis globe salvage rates and local control, Similarly, chromosome 8 gains and a
of retinoblastoma. Ongoing research the overall prognosis for this tumour loss of chromosome 1 are significantly
has shown a genetic and epigenetic continues to be grim. correlated with compromised survival.
landscape in RB using many techniques, Loss of chromosome 3 and polysomy
including higher resolution genomic Histopathology of Uveal of 8q are also associated with adverse
technologies, gene expression profiling, Melanoma morphological prognostic factors.
direct gene sequencing, multiplex-PCR, Conversely, gains in chromosome 6p
mi-RNA microarray profiling, next- Gross examination of the enucleated are linked with good prognosis25.
generation sequencing (NGS), DNA UM eyeball shows the location and size
methylation assays, microsatellite of the tumor, pattern of growth (dome- AJCC classification
analysis (MSA) for loss of heterogeneity shaped, mushroom-shaped, or diffuse), American Joint Committee on Cancer
(LOH), and in-situ hybridization for orbital involvement, the presence of (AJCC) classification (8th edition)
chromosomal aberrations. retinal detachment, and the degree of of primary tumor (T) is referred to
pigmentation. evaluate the clinical features and
Recently, Singh et al. studied the relevant prognosis of posterior uveal (ciliary
Histopathologically, they are of 3 cell body and choroid) melanoma26. There
role of the immunotherapeutic target types; spindle, epithelioid, or mixed are 2 separate pT classification systems
cell type. Kashyap et al., reported for uveal melanomas: one for the iris
such as PD-1/PD-L1 protein in primary spindle cell type to be the commonest and one for the ciliary body and choroid
type and has a better prognosis melanomas. Tumors with <50% of their
and chemoreduced RB where patient than epithelioid cell type21. HRFs volume located in the iris should be
include scleral invasion, ciliary body categorized using the ciliary body and
survival was reduced in cases of PD-L1 involvement, the nature of extracellular the choroid pT classification. Clinical
matrix patterns, number of infiltrating and pathological T categories are the
expressing primary retinoblastomas, macrophages and lymphocytes, same for UM.
microvascular density, and necrosis are
and PD-1 expressing chemoreduced found on hematoxin and eosin (H&E) Genetics
staining22. Immunohistochemically, In recent years, extensive research
retinoblastomas14. Berry et al. suggested they are reactive for S100, HMB-45, done on uveal melanoma yieldedthe
Vimentin, and/or MART-1/Melan-A is genetic background and its prognostic
liquid biopsy for identification of RB1 highly sensitive and specific for uveal significance.Gq alpha subunit
melanoma diagnosis. mutations, encoded by GNAQ and
variants in the aqueous humor cell- GNA11, have been found to be an early
Chromosomal Abnormalities or perhaps triggering events involving
free DNAthat predicts eye salvage in more malignant transformation
The most striking cytogenetic mutations in UM27. BRCA1-associated
retinoblastoma patients15. Andersch E abnormality in UM is a complete or protein-1 (BAP1) mutations, on the
partial loss of chromosome 3. Other other hand, tend to occur later and
et al. showed CD171- and GD2-specific common findings include loss of 1p, 6q, has a role in metastaticUM cases.
8,and9p, aswellasgainsof1q, 6p, and8q. Germline mutations of BAP1 may also
CAR-T cells as an important target for A gain of chromosome 6p has been seen occur, leading to a distinctive cancer
mainly in non-metastasizing tumors, predisposition syndrome.It appears
retinoblastoma cells in preclinical in whereas the converse situation applies that these mutations are crucial events
to a loss of chromosome 323. These
vitro testing16. Differentially expressed alterations were initially identified
proteins of mitochondrial dysfunction
and lipid metabolism pathways
have been found to be deregulated
in retinoblastoma tumor using mass
spectrometry-based quantitative
proteomic approach17. There are many
excellent models used for preclinical
studies of retinoblastoma, such as
zebrafish, murine, genetically modified
mouse and orthotopic human tumor
xenograft models.
Uveal Melanoma
Uveal melanoma (UM) is the most
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Subspeciality-Oculoplasty
that have the potential for being used 5. Singh L, Kashyap S. Update on pathology Ophthalmol. 2017;135(11):1221-30.
as a targeted therapy. Inactivation/ of retinoblastoma. Int J Ophthalmol.
loss of BAP1 is the most significant 2018;11(12):2011-6. 16. Andersch L, Radke J, Klaus A, Schwiebert
genetic alteration associated with poor S, Winkler A, Schumann E, et al.
prognosis in uveal melanoma28. Based 6. Jagadeesan M, Khetan V, Mallipatna A. CD171- and GD2-specific CAR-T cells
on metastasis, gene expression profiling Genetic perspective of retinoblastoma: potently target retinoblastoma cells in
(GEP) classification outperformed From present to future. Indian J preclinical in vitro testing. BMC Cancer.
clinical, pathological, and cytogenetic Ophthalmol. 2016;64(5):332-6. 2019;19(1):895.
prognostic indicatorsinto two groups
i.e. class 1 UM tumors (low risk), and 7. Dimaras H. Retinoblastoma genetics in 17. Danda R, Ganapathy K, Sathe G,
class 2 UM tumors (high risk), and this India: From research to implementation. Madugundu AK, Ramachandran S,
was verified by many research groups29. Indian J Ophthalmol. 2015;63(3):219-26. Krishnan UM, et al. Proteomic profiling
of retinoblastoma by high resolution
Deregulated Molecular Pathways 8. Thériault BL, Dimaras H, Gallie BL, mass spectrometry. Clinical Proteomics.
Corson TW. The genomic landscape 2016;13(1):29.
Recently, Jager et al. showed that of retinoblastoma: a review. Clin Exp
inflammation plays an important Ophthalmol. 2014;42(1):33-52. 18. Kashyap S, Meel R, Singh L, Singh M.
role in poor prognosis of UM30. The Uveal melanoma. Semin Diagn Pathol.
Canonical NFkB (C-NFkB) pathway is 9. Kashyap S, Sethi S, Meel R, Pushker N, 2016;33(3):141-7.
known to play a crucial role in tumor Sen S, Bajaj MS, et al. A histopathologic
inflammation. Singh et al. studied analysis of eyes primarily enucleated for 19. Singh AD, Bergman L, Seregard S.
the expression of NFkB proteins (p65, advanced intraocular retinoblastoma Uveal melanoma: epidemiologic
p50, and c-Rel) using immuno his to from a developing country. Arch Pathol aspects. Ophthalmol Clin North Am.
chemistry that activated the canonical Lab Med. 2012;136(2):190-3. 2005;18(1):75-84, viii.
NFkB pathway in high risk UM
patients31,32. Strong nuclear immuno 10. Sastre X, Chantada GL, Doz F, Wilson 20. Rietschel P, Panageas KS, Hanlon C,
expression of c-Rel suggests NFkB MW, de Davila MT, Rodríguez-Galindo Patel A, Abramson DH, Chapman
pathway activation which might be C, et al. Proceedings of the consensus PB. Variates of survival in metastatic
involved in the progression of UM33. The meetings from the International uveal melanoma. J Clin Oncol.
Rb and p53 pathways are functionally Retinoblastoma Staging Working 2005;23(31):8076-80.
inhibited in most UMs, although Group on the pathology guidelines for
mutations in the RB1 and TP53 genes the examination of enucleated eyes and 21. Kashyap S, Venkatesh P, Sen S,
are rare34. The PI3K/AKT and RAF/ evaluation of prognostic risk factors in Khanduja S, Shrey D, Tinwala S, et
MEK/ERK pathway is constitutively retinoblastoma. Arch Pathol Lab Med. al. Clinicopathologic characteristics
activated in a majority of UMs, and 2009;133(8):1199-202. of choroidal melanoma in a North
phosphorylated AKT correlates with Indian population: analysis of 10-year
poor prognosis in UM35. 11. Singh L, Pushker N, Sen S, Singh MK, data. International Ophthalmology.
Chauhan FA, Kashyap S. Prognostic 2014;34(2):235-9.
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3. Chantada GL, Qaddoumi I, Canturk WC. Retinoblastoma for Pediatric Anticancer Ther. 2006;6(4):493-506.
S, Khetan V, Ma Z, Kimani K, et al. Ophthalmologists. Asia Pac J
Strategies to manage retinoblastoma Ophthalmol (Phila). 2018;7(3):160-8. 25. Damato B, Dopierala JA, Coupland SE.
in developing countries. Pediatr Blood Genotypic profiling of 452 choroidal
Cancer. 2011;56(3):341-8. 14. Singh L, Singh MK, Rizvi MA, Bakhshi S, melanomas with multiplex ligation-
Meel R, Lomi N, et al. Clinical relevance dependent probe amplification. Clin
4. Abramson DH, Frank CM, Susman M, of the comparative expression of Cancer Res. 2010;16(24):6083-92.
Whalen MP, Dunkel IJ, Boyd NW, 3rd. immune checkpoint markers with the
Presenting signs of retinoblastoma. J clinicopathological findings in patients 26. Keung EZ, Gershenwald JE. The eighth
Pediatr. 1998;132(3 Pt 1):505-8. with primary and chemoreduced edition American Joint Committee
retinoblastoma. Cancer Immunol on Cancer (AJCC) melanoma staging
Immunother. 2020;69(6):1087-99. system: implications for melanoma
treatment and care. Expert Rev
15. Berry JL, Xu L, Murphree AL, Krishnan S, Anticancer Ther. 2018;18(8):775-84.
Stachelek K, Zolfaghari E, et al. Potential
of Aqueous Humor as a Surrogate Tumor 27. Inamdar GS, Madhunapantula SV,
Biopsy for Retinoblastoma. JAMA Robertson GP. Targeting the MAPK
pathway in melanoma: why some
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approaches succeed and other fail. outcome. J Cancer Res Clin Oncol. 35. Harbour JW. Genomic, prognostic,
Biochem Pharmacol. 2010;80(5):624-37. 2019;145(12):2969-82. and cell-signaling advances in uveal
melanoma. Am Soc Clin Oncol Educ
28. Harbour JW, Onken MD, Roberson 32. Singh MK, Singh L, Pushker N, Saini N, Book. 2013:388-91.
ED, Duan S, Cao L, Worley LA, et Meel R, Chosdol K, et al. Identification
al. Frequent mutation of BAP1 in of canonical NFkB (C-NFkB) pathway in Corresponding Author:
metastasizing uveal melanomas. uveal melanoma and their relation with
Science. 2010;330(6009):1410-3. patient outcome. Clin Exp Metastasis. Dr. Seema Kashyap MD
2019;36(3):271-90. Department of Ocular Pathology
29. Onken MD, Worley LA, Ehlers JP, Ophthalmology Services,
Harbour JW. Gene expression profiling in 33. Singh MK, Singh L, Pushker N, Dr. R. P. Centre for Ophthalmic Sciences,
uveal melanoma reveals two molecular Chosdol K, Bakhshi S, Meel R, All India Institute of Medical Sciences,
classes and predicts metastatic death. et al. Constitutive expression of New Delhi, India
Cancer Res. 2004;64(20):7205-9. c-REL in uveal melanoma patients:
correlation with clinicopathological
30. Bronkhorst IH, Jager MJ. Inflammation parameters and patient outcome.
in uveal melanoma. Eye (Lond). Clinical and Translational Oncology.
2013;27(2):217-23. 2020;22(7):1193-204.
31. Singh MK, Singh L, Chosdol K, Pushker 34. Brantley MA, Jr., Harbour JW.
N, Saini N, Meel R, et al. Differential Deregulation of the Rb and p53
expression of p52 and RelB proteins pathways in uveal melanoma. Am J
in the metastatic and non-metastatic Pathol. 2000;157(6):1795-801.
groups of uveal melanoma with patient
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Subspeciality-Oculoplasty
Orbital Implants: An Overview
Anju Bhari MD, Gunjan Saluja MD, Neelam Pushker MD
Oculoplasty, Tumor & Pediatric Ophthalmology Services,
Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
Abstract: Orbital implants are placed in the orbit after enucleation and evisceration. Various types of designs and materials have been
used for orbital implants. The aim of this article to discuss about various orbital implants and their classification. This article also highlights
important points for deciding size of the implant and for using implants in children and in panophthalmitis patients after surgery.
History Orbital implants are placed in the orbit the implant. Mules implant is a non-
There have been several advances in the after enucleation/evisceration to: integrated implant, which is the most
development of designs and materials of basic solid, smooth surface, spherical
orbital implants since the introduction • To replace the lost orbital volume. implant, composed of polymethyl-
of the first implant. In 1885, Mules • To support and provide good methacrylate (Figure 1A). Advantages
used spherical hollow implants of glass of Mules implant are that it is cheap,
after evisceration. In 1945, Ruedemann motility to the prosthesis. easily available and have smooth
described exposed integrated implant • To prevent post-enucleation socket surface which avoids irregular pressure
which was a combined motility implant on tissue anterior to it and decreases
and ocular prosthesis. In 1947, Cutler syndrome. risk of implant exposure. Disadvantages
introduced another exposed integrated • To promote orbital growth in are poor motility and increased risk of
implant. High risk of infection, mostly implant migration (Figure 1B).
within 2-3 years, made these implants paediatric post - enucleation 2. Integrated implants
obsolete. In1950s, various semi- patients. Integrated implants had exposed
integrated implants like Allen, Iowa and Classification conjunctival surface to directly fit
universal implants were described1,2. Earlier, orbital implants were classified with the customized posterior surface
Hydroxyapatite orbital implants were as non-integrated, integrated, and semi- of the prosthesis. In 1947, Cutler
described by Perry in 19853. Synthetic integrated. introduced methyl-methacrylate, ball
porous polyethylene and aluminum and ring implant. The exposed surface
oxide implants were described in 2000s. 1. Non-integrated Implants
In non-integrated implant, extra-ocular
muscles cannot be directly attached to
(a) (b)
Figure 1(a): Mules implant. (b): Patient with inferiorly migrated Mules implant in the left eye.
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Subspeciality-Oculoplasty
had a square defect for square peg prosthesis for proper fitting to match pegged. The major limitation of porous
of the prosthesis. The recti muscles the anterior contour of implant. implants is high cost.
were looped around and sutured to
the ring4. Due to severe complications The above mentioned classification a) Hydroxyapatite Implant (Bio-Eye,
like frequent implant extrusion led to confusion on use of the term, FCI3)-
and infection, these implants were ‘integrated’. Word ‘integrated’ was
discontinued. used interchangeably either for Hydroxyapatite was approved for use as
attachment of extra-ocular muscles to an orbital implant by FDA in 1989. These
3. Semi-integrated Implants the implant or for the direct physical are porous implant which are obtained
coupling of implant with the artificial from natural corals (Bio-Eye) after
Semi-integrated implants allow eye. In year 2002, a scientific panel of hydrothermal exchange reaction which
attachment of extraocular muscles the American Society of Ocularists converts CaCO3 into Ca10(PO4)6 (OH)2.
in tunnels/grooves on their anterior (ASO) and American Academy of Its architecture is similar to cancellous
surface for better motility. These Ophthalmology (AAO) came to a bone with numerous interconnecting
implants are made of polymethyl- consensus that the word ‘integration’ pores of 200-500 millimeters diameter
methacrylate and types are, Allen, Iowa, refers to the nature of fit between which allows fibrovascular ingrowth
and Universal implants. prosthesis and implant. Attachment and tissue integration. The surface of
of extraocular muscles to the implant these implants is rough which increases
a. Allen implant: This implant has does not imply integration. the risk of implant exposure. To
an anterior ring with tunnels and a decrease the risk of early exposure, the
posterior spherical segment. The recti The implants were re-classified as: implant needs to be wrapped. Because
muscles are passed through the tunnels of easy availability, banked sclera is
and sutured. Due to the flat apposition 1. Buried implants: Smooth apposition commonly used wrapping material.
between implant and prosthesis, there is present between the implant Cutting windows into the sclera at the
is higher rate of late implant exposure and the prosthesis with intact site of attachment of the recti muscles
and also translation of movements is conjunctiva in between them. can facilitate faster vascularization. The
not too good with torsional end gaze Example: Mules implant, Silicon sclera incites a foreign body reaction
movements. implant. and gets absorbed over time, which is
associated with late exposure. So, use
b. Iowa implant: This implant has 4 2. Exposed-integrated implants: Direct of autologous grafts like temporalis
peripheral mounds of 5mm height attachment is present between the fascia, fascia lata and synthetic material
on the anterior surface. The mounds implant and the prosthesis with such as polyglactin mesh, have also
correspond to depression on the back interrupted conjunctival lining in been described. The main disadvantage
surface of prosthesis. The muscles are between them. Example: Cutler of natural coral-made implant (Bio-
brought together through the valleys implant. eye) is high cost, so synthetic form of
in between the mounds and tied at hydroxyapatite (FCI3) was introduced
a central anterior depression. This 3. Buried-integrated implants: The which is cheaper and can also be easily
implant has lower extrusion rate (3.3%) posterior surface of the prosthesis drilled6.
than Allen implant. is modified to fit with the anterior
surface of the implant to improve b) Porous Polyethylene Implant
c. Universal implant: The mounds the transfer of the implant (Medpore, Biopore) -
on this implant are lower and more movement to the prosthesis
rounded than Iowa that decrease the movement with intact conjunctiva These implants are formed from
risk of localized pressure necrosis and in between them. Example: Allen, polymerization of ethylene molecules
implant exposure than Allen and Iowa Iowa and Universal implant. under high temperature and pressure
implant.2 which creates straight chains called
Porous Implants as polyethylene. They are also porous
Important disadvantages of semi- and allow fibro-vascular ingrowth.
integrated implant, because of which With the introduction of porous They have smoother surface than
they lost their popularity are - irregular implants came the term ‘bio-integration’ hydroxyapatite and aluminum oxide
anterior surface causing conjunctiva which is used for biological integration implants, so less risk of implant
and Tenon’s capsule to be pinched of implant with orbital tissues due exposure.7 The wrapped and
between implant and prosthesis that to fibrovascularization ingrowth, unwrapped porous polyethylene
increases risk of late implant exposure, examples are - hydroxyapatite, porous implants have similar exposure rates
and need of special customized polyethylene, and aluminium oxide
implants. It falls under the category
of buried implants till the time it is
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Subspeciality-Oculoplasty
(<5%), so wrapping can be avoided.8 if pegged. Disadvantages of porous Sizing of Implant
Muscles can be directly sutured with implants are high cost and increased
the implant. These features drastically risk of implant exposure because of The average orbital volume loss after
reduce the surgical time and make it rough surface. All the porous implants enucleation is 7-9 ml. Size of orbital
the most preferred porous implant. can be pegged, to improve the motility implant is chosen such that the 70-80%
The coralline hydroxyapatite implants of the prosthesis. Earlier polycarbonate of lost volume is replaced by implant.
need drilling for peg placement, but pegs were used. In recent years, This allows for a prosthetic volume
porous polyethylene implants can be titanium peg and sleeve systems have of around 2 – 2.5 ml. The upper limit
pegged by hand with a screwdriver. been preferred because of the decreased of prosthetic volume has been found
Though the commonly used type is risk of extrusion and granuloma to be 4.5ml in recent studies. Larger
simple sphere, but these implants are formation. Pegs can be placed when prosthesis can cause complications
also available in a number of shapes, the vascularization of implant is like lower lid laxity and malposition
such as conical orbital implant with complete, which usually takes 10 – 12 due to over-weight and limited socket
a 6mm flat anterior surface (Dresner), months. Gadolinium enhanced MRI excursion13.
smooth surface tunnel sphere (SST) is the preferred method of assessment
with suture tunnels for muscle of implant fibrovascularization till the There are various methods used for
attachment, conical orbital implant center of the implant. Pegging is done by determination of size of the implant
with a superior projection to decrease ocularist under the guidance of treating with basic principle that grossly,
superior sulcus defect. To reduce surgeon. Most surgeons avoid pegging 2/3rd eyeball volume to be replaced
the risk of exposure, implant with of the implant due to comparable by implant and 1/3rd volume left for
modified smooth anterior surface is results even without pegging, high prosthesis. Various methods described
also available Further, some surgeons cost and peg related complications. for assessment of eyeball volume
prefer to cover the anterior surface In a study on 100 patients, authors are by measurement of - axial length
with orbital fat or sclera cap to reduce reported complications in 48% cases of the contralateral eye; diameter
erosion of overlying conjunctiva. that included discharge, peg extrusion, of the enucleated globe, and water
granulomas, popping peg, peg drilled displacement by the enucleated
c) Aluminum Oxide Implant (Alumina)- off centre and excess movement of the globe using graduated cylinder. Intra-
peg10. operative assessment after placing the
Aluminum oxide implants are porous implant is also important. This can be
implants with improved connectivity Biogenic Graft done by passing a center test suture
between pores which increases and placing proper size conformer and
vascularization. These implants need Dermis Fat Graft (DFG ) - Smith and compare the prominence of normal eye
to be wrapped like hydroxyapatite Petrelli first described DFG for an with the operated side, with closed lids,
implant. They are light weight and can anophthalmic socket reconstruction from head end. Further, after placing the
be easily drilled out without crumbling. in 1978. It is an autologous implant test suture, if the conjunctival surface is
Earlier, one of the major concerns with consisting of de-epithelized epidermis not convex i.e. it is flat; or the sutures
the use of this implant was aluminum with its adjacent subcutaneous fat are under tension then it is important
toxicity but aluminum oxide does not tissue taken from upper outer quadrant to replace the implant, larger in former
release soluble aluminum. Jordan et al of gluteal region. Advantages of DFG scenario and smaller in later.
described a case series of 107 patients are that it’s an autologous tissue that
with aluminum oxide implants. The augments both orbital volume and It is important to have 2-3 different
implant was well tolerated by most surface area11. Disadvantages are donor sizes of desired implant in the operation
of the patients. The complications site complications, necrosis or infection theatre with preferably Mules implants
reported were discharge (5%), implant of the graft, etc. of different sizes to assess the exact size
exposure (2%), and socket discomfort during surgery. After assessing the size,
(1%) and conjunctival thinning (2%). Hydrogel Implant Mules implant can be replaced by the
Peg related complications were found same size implant we desire to place.
in 34.3%9. These implants are composed of methyl- Generally, in adults, after enucleation
methacrylate and N-vinylpyrrolidone. 20-22 mm spherical implants are
Advantages of porous over non-porous They are solid hydrophilic tissue used and after evisceration, 18-20 mm
implants are that porous implants expanders. They are small and solid in implants are used. After evisceration,
provide better stability i.e. it is dehydrated state and expand slowly sclera (of around 1mm thickness) is
associated with minimal migration, and when hydrated. They are used for the left intact which decreases the size of
also provide better prosthetic motility, expansion of congenital anophthalmic the required implant by about 2mm. In
sockets12.
82 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times
Subspeciality-Oculoplasty
children, usually 16-18 mm implants surface can be cleaned with wet cotton and prosthesis motility was best in
are used depending upon on the age or soft cloth, when needed. the PMMA-myoconjunctival group15.
and orbital bone development of the Most of the studies have shown similar
patient. The average volume replaced Implants in Children motility and complications rates in
by 16mm, 18mm and 20mm orbital The use of porous implants in children porous (without pegging) vs. non-
implant is around 2.1 ml, 3.1 ml and 4.2 of less than 2-3 years especially infants porous implants16.
ml respectively. is avoided as exchange of these implants
with larger size implant for volume References
Motility of Ocular Prosthesis augmentation is difficult due to bio-
integration. Use of acrylic ball implant 1. Spivey BE, Allen LH, Burns CA. The
Prosthesis motility in absence of (Mules) or silicone implant is preferred Iowa enucleation implant: a ten year
pegging is mainly due to the deepening as replacement can be done easily, if evaluation of techniques and results.
of conjunctival fornices due to needed. Am J Ophthalmol. 1969;67:171–181.
extraocular muscle contraction during In older children with adequate growth
contralateral eye movements, according of orbital cavity, porous implants can 2. Jordan DR, Anderson RL, Nerad JA,
to the Herrings law. The deepening be safely placed. Its use has also been Allen L. A preliminary report on the
of fornix leads to shallowness of advocated in retinoblastoma patients universal implant. Arch Ophthalmol.
opposite fornix, which then pushes the as its presence is not known to interfere 1987;105:1726–1731.
prosthesis in the direction of deepened with radiation therapy and detection
fornix. Nowadays, myoconjunctival of recurrence on MRI. The porous 3. Perry AC. Advances in enucleation.
technique of enucleation is preferred, in implant is also associated with almost Ophthalmic Plast Reconstr Surg. 1991;
which recti muscles are sutured to the nil migration unlike the Mules implant. 4:173–182.
conjunctival fornices to improve the
motility of the prosthesis. Motility of Implants in Panophthalmitis 4. Cutler NL: A positive contact ball
the prosthesis decreases in the absence Earlier, the concept was that primary and ring implant. Arch Ophthalmol .
of the implant, as some amount of placement of orbital implant after 1947;37:73-77.
movements is also due to snugly fit of enucleation or evisceration for
prosthesis with the convexity of the fulminant ocular infection should be 5. David Sami, Steven Young, Robert
implant. The lid position also depends avoided because it was thought to be Petersen. Perspective on Orbital
on the presence and size of implant. associated with higher risk of implant Enucleation Implants. Survey of
exposure, extrusion and persistence of Ophthalmology. 2007;52(3):244-265.
Ocular Prosthesis infection. But recent studies have shown
that primary porous and non-porous 6. Jordan DR, Gilberg S, Mawn L, et
An ocular prosthesis is generally placed implant placement after surgery for al: The synthetic hydroxyapatite
after 6 weeks of the surgery and proper ocular infection is not associated with implant: a report on 65 patients.
tissue healing. Artificial eye used after increased risk of complications and it OphthalPlastReconstr Surg. 1998;14:250-
enucleation and evisceration can be also decreases the cost and discomfort 255.
custom made eyes or stock (ready- to the patient14.
made) eyes. Custom made artificial 7. Jordan DR, Brownstein S, Dorey M,
eyes are designed according to the Choice of Orbital Implant et al: Fibrovascularization of porous
individual anophthalmic socket by Worldwide, porous implants are polyethylene (Medpor) orbital implant
modified impression technique. They preferred in patients undergoing in a rabbit model. Ophthal Plast Reconstr
give better cosmetic match and motility enucleation or evisceration procedure Surg. 2004;20:136-143.
but are costly. Due to lack of proper mainly because of their stability and
fitting in stock eyes, they can cause bio-integration. High cost of porous 8. Blaydon SM, Shepler TR, Neuhaus RW,
complications like chronic discharge, implant is the major limitation in et al: The porous polyethylene (Medpor)
pyogenic granuloma formation and non-affording patients where silicone spherical orbital implant: a retro-
implant exposure. The stock eye needs or Mules implant can be used. In a spective study of 136 cases. Ophthal
to be replaced after every 1-2 years studied conducted on 150 patients who Plast Reconstr Surg. 2003;19:364-371.
because its surface becomes rough or underwent enucleation, it was observed
irregular. Custom made eyes can be that the implant motility was better 9. Jordan DR, Gilberg S, Mawn LA. The
used for a longer period of time. Regular in the PMMA-myoconjunctival and Bioceramic Orbital Implant: Experience
polishing of artificial eye artificial porous polyethylene groups compared With 107 Implants. Ophthalmic
by ocularist keeps socket healthy. to PMMA with muscle imbrication, Plastic and Reconstructive Surgery.
Everyday removal of artificial eye for 2003;19(2):128-135.
cleaning is not advisable instead its
10. Lin CJ, Liao SL, Jou JR et al. Complications
of motility peg placement for porous
hydroxyapatite orbital implants. Br J
Ophthalmol. 2002;86:394-396.
11. Bhattacharjee K, Bhattacharjee H,
Kuri G, Das JK, Dey D. Comparative
analysis of use of porous orbital
implant with mucus membrane graft
and dermis fat graft as a primary
procedure in reconstruction of severely
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Subspeciality-Oculoplasty
contracted socket. Indian J Ophthalmol. 14. Abel AD, Meyer DR. Enucleation with Corresponding Author:
2014;62(2):145-153. Primary Implant Insertion for Treatment
of Recalcitrant Endophthalmitis Dr. Anju Bhari MD
12. Mazzoli RA, Raymond WR, 4th, and Panophthalmitis. Ophthalmic Oculoplasty, Tumor & Pediatric
Ainbinder DJ, Hansen EA. Use Plastic and Reconstructive Surgery. Ophthalmology Services,
of self-expanding, hydrophilic 2005;21:220-226. Dr. R. P. Centre for Ophthalmic Sciences,
osmotic expanders (hydrogel) in the All India Institute of Medical Sciences,
reconstruction of congenital clinical 15. ShomeD,HonavarSG,RaizadaK,Raizada New Delhi, India
anophthalmos. Curr Opin Ophthalmol. D. Implant and prosthesis movement
2004;15:426–31. after enucleation: a randomized
controlled trial. Ophthalmology.
13. Jordan DR, Klapper SR. Enucleation, 2010;117:1638-1644.
Evisceration and Secondary Orbital
Implantation. In: ServatJJ, Black EH, 16. Ho VW, Hussain RN, Czanner G et
Nesi FA, Gladstone GJ, Calvano CJ, eds. al.Porous versus nonporous orbital
Smith and Nesi’s Ophthalmic Plastic implants after enucleation for uveal
and Reconstructive Surgery. 4th ed. melanoma: a randomized study. Ophthal
Switzerland, CH:Springer Nature Plast Reconstr Surg. 2017;33(6):452-458.
Switzerland AG;2020:1029-1054.
84 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times
Subspeciality-Oculoplasty
Orbital Fungal Infections
Gunjan Saluja, MD, DNB, Sujeeth Modaboyina, MD, Neelam Pushker MD
Oculoplasty, Tumor & Pediatric Ophthalmology Services,
Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
Abstract: Orbital fungal infections are an important cause of ocular morbidity. Orbital mucor mycosis and orbital aspergillosis are the
common causes of orbital fungal infection in the tropical countries. The infection begins from the sinuses with gradual involvement of the orbit
and central nervous system involvement in the late stages, thus requiring a multi-disciplinary approach. The article describes the common
clinical features, imaging findings and management options for the common orbital fungal infections.
Fungal infections of orbit usually Pathogenesis the distribution of ophthalmic and
develop secondary to sinus In an immunocompetent individual, maxillary division of the trigeminal
involvement and results in significant the fungal spores are phagocytosed nerve are danger signs and suggest
ocular morbidity as well as have high by the macrophages and polymorphs; the development of cavernous sinus
mortality. Fungi are saprophytic further are killed by the oxidative thrombosis with a poor prognosis.
organisms residing in the dead decaying stress caused due to generation (Figure A) Lateral rectus palsy due to 6th
vegetative matter and soil and enter of free radicals. This prevents the cranial nerve involvement is one of the
through the respiratory route in the further spread of infection. However, first nerves to be involved in cavernous
form of spores. The usual source in immunocompromised patients, sinus thrombosis. Visual acuity is no
of orbital fungal infection is either there is a decrease in chemotaxis and perception of light in most of the cases
from the surrounding sinus or direct phagocytosis by macrophages and due to central artery occlusion2. The
inoculation after trauma. The orbital polymorphs. Acidic pH and an increase involvement of 3rd, 4th, and 6th cranial
fungal infections are most commonly in the levels of free iron in patients with nerves at the orbital apex leads to
caused by Mucor sp. and Aspergillus diabetic ketoacidosis also promotes paralytic squint, along with progressive
sp. Fusarium, Scedosporium, the survival of spores. A characteristic vision loss due to the involvement of the
Entomophthoramycosis,Blastomycosis, feature of mucormycosis is the optic nerve leading to relative afferent
Candida are some of the rare causes. presence of extensive angioinvasion pupillary defect (RAPD). The presence
which results in thrombosis and tissue of black eschar suggests necrosis of
Mucormycosis necrosis. Angioinvasion also promotes tissues, specifically present in the
the hematogenous spread of infection nasopharynx, oropharynx, and in the
Orbital mucormycosis is caused by from the original site to other target later stages in the periorbital area. The
the subset of Zygomycosis which organs. presence of black eschar is almost always
includes Mucor, Rhizopus, Absidia. pathognomonic of mucormycosis in
Mucormycosis is an aggressive infection Clinical Presentation patients with uncontrolled diabetes and
affecting mainly immunocompromised The initial symptoms are due to immunocompromised conditions.
individuals, with the overall incidence sinusitis or orbital cellulitis and include
being 0.15% amongst diabetics. The facial or ocular pain this is followed by Diagnosis
complications associated with infection conjunctival congestion, blurry vision, Imaging
like cavernous sinus thrombosis soft tissue swelling, and foul-smelling
and the central nervous system discharge. Infection from sinuses Magnetic resonance imaging (MRI)
spread are mostly fatal. Individuals can spread to the orbit, resulting in with contrast demonstrates variable
with hematological malignancies, proptosis with orbital apex syndrome. T1 and T2 intensity with devitalized
diabetic ketoacidosis, prolonged Rhino-orbital-cerebral disease occurs in mucosa appearing as contiguous foci
immunosuppression therapy after up to half of all the patients1. of non-enhancing tissue, seen as a black
organ transplant surgeries, HIV turbinate sign. T1 shows isointense
infection are predisposed to develop Bilateral proptosis, chemosis, lesions in ~80% of cases, T2 is variable
orbital mucormycosis. diplopia, and loss of sensation along with around 20% of patients showing
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Subspeciality-Oculoplasty
hyperintensity signals3. Orbital essential in diabetic patients. 14-demethylase, with a higher affinity
imaging shows the presence of diffuse and fewer systemic side effects. The
involvement reaching up to the orbital Antifungal therapy spectrum of posaconazole is large with
apex with a lack of enhancement. Polyenes are the first choice of drugs in vitro activity against various fungal
(Figure B) Cavernous sinus thrombosis for the treatment of mucormycosis. pathogens like Aspergillus, Candida,
presents as a hyperintense lesion. Amphotericin B (AmB) acts by Mucor, Fusarium species. Zygomycetes
Contrast-enhanced computed increasing the permeability of the fungal resistant to other azoles also has
tomography scan (CECT) shows a cell membrane. Lipid formulations of shown response to posaconazole. The
lack of enhancement in the cavernous AmB are significantly less nephrotoxic formulation of posaconazole is a 40
sinus region with a rim of thickened and can be safely administered at mg/ml oral suspension containing
soft tissue along the paranasal sinuses. higher doses for a longer period with polysorbate as an emulsifying agent. It
Other important findings include the better outcomes4,5. After sensitivity is usually administered at oral dosage of
opacification of the paranasal sinuses, testing liposomal amphotericin B is 800 mg per day, in two or four divided
fluid levels in the sinuses, and bony administered intravenously in the dose doses. Recently, the injectable form of
destruction. However, these findings of 5mg/kg/day, in 5% dextrose for 6 posaconazole is also available, which is
are nonspecific. weeks, followed by oral posaconazole administered in a dose of 300 mg every
400mg twice a day6. 12 hours was required9.
Potassium hydroxide staining
(KOH staining) Direct drug delivery Caspofungin
A few case reports have demonstrated Combination polyene-caspofungin
KOH staining of deep scrapings and the efficacy of direct drug delivery by therapy has been shown to have a
biopsies of involved tissue appearing the means of direct irrigation of sino- promising potential alternative to
as black eschar in the paranasal orbital tissues with 5ml amphotericin polyene monotherapy for patients with
sinus, nasal cavity, nasopharynx or B 1mg/ml and retrobulbar injections of invasive orbital mucormycosis10.
oropharynx should be done as an 1ml of 3.5mg/ml AMB deoxycholate as
emergency procedure. The presence an adjunct to systemic antifungals and Isavuconazole
of broad, irregular, ribbon-like, non- sinus debridement7,8. The beneficial Isavuconazole is a novel triazole
septate, and right-angled branching effect of direct drug delivery is with the mode of action similar to
hyphae suggests mucormycosis hypothesized by the angio-invasive voriconazole but, has a broad spectrum
(Figure C). The fungal invasion may nature of the disease that limits tissue of activity encompassing a wider range
be patchy, so multiple and deeper penetration of systemic antifungals. of fungal species, including Mucorales.
biopsies may be required. Histological However, long term results of these Isavuconazole has demonstrated blood-
examination of biopsy tissue shows methods are still not known. brain barrier penetration in animal
characteristic angio-invasion and tissue models. The drug also is efficacious as
infarction. Fungal hyphae can also be Surgical management primary therapy in patients infected
demonstrated with Grocott-Gomori Aggressive surgical debridement of with rare fungi.
methenamine–silver nitrate, periodic infected tissues should be done as early
acid–Schiff, or calcofluor white stain. as possible. Exenteration is usually The drug is administered in the
(Figure D) Sabouraud dextrose agar required to prevent the spread of intravenous dose of 200 mg every 8
culture helps in the characterization of infection in extensive orbital disease hours for six doses, followed by 200 mg
fungal species. involving orbital apex. (Figure D) orally once daily starting 12 to 24 hours
The extent of orbital disease, salvage after the last loading dose. The common
Treatment ability of the eye, likelihood of further side effects reported are gastrointestinal
Management of orbital mucormycosis spread, and general condition of the side effects, with a lower incidence of
involves a multidisciplinary approach patient needs to be considered before hepatotoxicity as compared to other
and requires the combined efforts of the procedure. Functional endoscopic azoles. The side effects are reversible
an endocrinologist, ophthalmologist, sinus surgery can be performed by the and do not require discontinuation of
neurosurgeon, microbiologist, and otolaryngologist. The mortality rate the drug11.
an otolaryngologist. Intravenous of Rhino-orbital cerebral disease is 30-
amphotericin B preferentially 50%. Hyperbaric oxygen
liposomal along with prompt radical Hyperbaric oxygen acts by increasing
surgical debridement of necrotic tissues Posaconazole oxygenation, decreasing acidosis, and
is the mainstay of management. Posaconazole is an azole, which increasing the phagocytic activity.
inhibits the ergosterol production by Hyperbaric oxygen can also be used as
Controlling blood sugar levels and binding and inhibiting the lanosterol- an adjunct to amphotericin B.
management of diabetic ketoacidosis is
86 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times
Subspeciality-Oculoplasty
Orbital Aspergillosis
The fungi are present in the soil
and dead decaying matter and gains
access through the respiratory route.
The disease course in aspergillosis is
benign and indolent as compared to
mucormycosis.
Orbital aspergillosis is usually caused
by Aspergillus flavus and Aspergillus
fumigatus. Studies from western
countries have reported Aspergillus
fumigatus as the most common
agent, while Asian countries report
Aspergillus flavus as the main causative
agent12.
Aspergillus flavus is common in
immunocompetent individuals,
whereas Aspergillus fumigatus is
common in immunocompromised
patients13. The localized form of
invasive aspergillosis affects more
commonly immunocompetent
individuals as reported from the Indian
sub-continent14.
Patterns of orbital involvement Figure A: Patient of bilateral sino-orbital mucormycosis, with bilateral proptosis and
necrosis of overlying skin
Patterns of involvement of orbital Figure B: MRI axial view showing pansinusitis with diffuse orbital soft tissue involvement
aspergillosis depend on the causative reaching upto orbital apex
agent and the immune status of the Figure C: KOH stain of the biopsy showing broad, irregular, ribbon-like, non-septate, hyphae
patient. Patients usually present with with right-angled branching
painless proptosis with an ill-defined Figure D: Exenterated socket in the post-operative period in a patient of orbital mucormycosis
sino-orbital mass lesion on imaging. A. Figure E: Patient of orbital aspergillosis, sagittal view of CT showing the localized
flavus causes an invasive granulomatous involvement
infection with the localized sino-orbital Figure F: KOH stain showing acute-angled branching septate hyphae
disease., whereas A. fumigatus may
present as a non-invasive or invasive Investigation hyperdense infiltrating lesion in the
necrotizing-fulminate infection. The Invasive orbital aspergillosis usually orbit. Calcification>2000 Hounsfield
presenting symptoms of a localized presents as the sino-orbital disease. unit in the surrounding ethmoid and
form of invasive orbital aspergillosis The imaging findings can masquerade sphenoid sinuses is pathognomonic
include chronic, dull retrobulbar pain malignancy, IgG4 related orbital for the diagnosis of aspergillosis12 CT
for months, associated with headache, disease, and other granulomatous scan also helps in early diagnosis of
mild redness, and proptosis, which disorders. Contrast-enhanced CT bony erosion. MRI helps to diagnose the
progress to involve the orbital apex of orbit demonstrates the presence presence of sinus mucosal thickening,
and cranial nerves if left untreated. In of an ill-defined heterogeneous, the extent of soft tissue involvement,
the late stages of the disease, invasive cavernous sinus thrombosis, and
orbital aspergillosis may result in orbital
apex syndrome, necrotizing angiitis,
thrombosis, systemic dissemination,
erosion of the orbit, and direct invasion
of the central nervous system, especially
in immunocompromised and untreated
patients.
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Subspeciality-Oculoplasty
intracranial involvement. (Figure E) twice for 1 day followed by 4 mg/kg edition Philadelphia: Saunders; 3rd
To confirm the diagnosis, a biopsy twice per day for 1-2 weeks, followed edition. 2008; Infectious Processes of
is required. The transnasal biopsy is by oral voriconazole at a dose of 200 mg Orbit;pp297-2969.
easier to obtain than an orbital biopsy twice daily if the bodyweight is >40kg
especially in lesions beyond mid-orbit. or 100 mg if bodyweight is <40 kg19. The 2. Bhansali A, Bhadada S, Sharma A, Suresh
Orbital fine-needle aspiration biopsy common side effects of voriconazole V, Gupta A, Singh P, Chakarbarti A,
depends upon the yield of tissue. are gastrointestinal side effects, Dash RJ. Presentation and outcome of
Fungi on KOH staining appear as 45° hepatotoxicity, and vision disturbances rhino-orbital-cerebral mucormycosis in
branching septate hyphae, 2–4 µm in like light sensitivity and blurry vision. patients with diabetes. Postgrad Med J.
width. Sabouraud dextrose agar culture Oral itraconazole can also be used as a 2004 Nov;80(949):670-4.
helps in the characterization of fungal substitute for oral voriconazole at a dose
species (Figure F). of 200 mg twice. There is no uniform 3. Herrera DA, Dublin AB, Ormsby EL,
consensus about the duration of the Aminpour S, Howell LP. Imaging
Role of Serum Galactomannan administration of antifungal drugs. findings of rhinocerebral mucormycosis.
Galactomannan (GM) is a Long-term administration is usually Skull Base. 2009;19(2):117-125.
polysaccharide cell wall component reported. Intravenous amphotericin B
of Aspergillus sp. released by growing (1mg/kg in 5% dextrose for 6 weeks) 4. Walsh TJ, Hiemenz JW, Seibel NL, Perfect
hyphae. It is used as a biomarker in can be considered in patients with side JR, Horwith G, Lee L, Silber JL, DiNubile
the diagnosis of systemic invasive effects of voriconazole or who are not MJ, Reboli A, Bow E, Lister J, Anaissie
aspergillosis especially in patients with able to afford the drugs or in patients EJ. Amphotericin B lipid complex for
hematological malignancy. Plateia with mixed infections. Posaconazole in invasive fungal infections: analysis of
Aspergillus enzyme immunoassay aspergillosis is helpful in patients who safety and efficacy in 556 cases. Clin
(EIA, Bio-Rad Laboratories, Hercules, are resistant to conventional treatment. Infect Dis. 1998 Jun; 26(6):1383-96.
CA, USA) is used to detect GM
concentrations in the body fluids. The Surgical management 5. El Zein S, El-Cheikh J, El Zakhem A,
result is expressed as a galactomannan Exenteration is usually not required in Ibrahim D, Bazarbachi A, Kanj SS.
index (GMI). As GMI directly depends patients with orbital aspergillosis, as Mucormycosis in hospitalized patients
on the amount of antigenemia, most of the patients with a localized at a tertiary care center in Lebanon: a case
hence, serial measurements of serum form of invasive aspergillosis of series. Infection. 2018 Dec;46(6):811-821.
galactomannan help to monitor the orbit or sino-orbit respond
treatment response. GMI more than 0.5 to the medical management and 6. Karadeniz Ugurlu S, Selim S, Kopar A,
is considered to be significant. debridement. There is no consensus Songu M. Rhino-orbital Mucormycosis:
Its utilization in invasive orbital about the role of exenteration in Clinical Findings and Treatment
aspergillosis is yet to be explored16. orbital aspergillosis. Sinus debridement Outcomes of Four Cases. Turk J
is done by otolaryngologists and Ophthalmol. 2015;45(4):169-174.
Management orbital debridement is rarely
Voriconazole is a second-generation needed in progressive or fulminant 7. Joos ZP, Patel BC. Intraorbital Irrigation
triazole antifungal and is the first line disease. Prognosis remains poor in of Amphotericin B in the Treatment
of the drug in the treatment of invasive immunocompromised individuals of Rhino-Orbital Mucormycosis.
aspergillosis. It has proven to have better with invasive sino-orbital aspergillosis. Ophthalmic Plast Reconstr Surg.
efficacy and fewer side effects than Few reports also describe the role 2017;33(1):e13-e16.
amphotericin B in systemic invasive of retrobulbar injections and local
aspergillosis. A survival benefit of 13% irrigation of orbital tissues with 8. Hirabayashi KE, Kalin-Hajdu E, Brodie
has been reported over amphotericin amphotericin B as an adjunct to FL, Kersten RC, Russell MS, Vagefi MR.
B.17Literature reports a response rate systemic antifungals and sinus Retrobulbar Injection of Amphotericin B
of 40-60% with amphotericin B and debridement in the management of for Orbital Mucormycosis. Ophthalmic
most patients are unable to tolerate orbital aspergillosis20,21. Plast Reconstr Surg. 2017;33(4):e94-e97.
prolonged therapy due to serious side- Acknowledgment: Dr. Nishat
effects like nephrotoxicity18. Nowadays Hussain, Ocular Microbiology, Dr.R.P. 9. European Medicines Agency,
amphotericin B is used as a second-line Centre, AIIMS, New Delhi. Committee for Medicinal Products for
drug in the management of invasive Human Use Assessment report.Noxafil.
aspergillosis. The usual dosage of References EMA/159150/2014.
voriconazole administered is a loading 1. Albert DM,. Jakobiec FA, eds. Principles
dose given intravenously of 6 mg/kg 10. Reed C, Bryant R, Ibrahim AS, Edwards
and Practice of Ophthalmology. 3rd J Jr, Filler SG, Goldberg R, Spellberg
B. Combination polyene-caspofungin
treatment of rhino-orbital-cerebral
mucormycosis. Clin Infect Dis. 2008 Aug
1;47(3):364-71.
11. MartyFM, Ostrosky-ZeichnerL, Cornely
OA et al. Isavuconazole treatment for
mucormycosis: a single-arm open-label
trial and case-control analysis. Lancet
Infect Dis. 2016; 16: 828–837
12. Pushker N, Meel R, Kashyap S, Bajaj MS,
Sen S. Invasive aspergillosis of orbit in
88 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times
Subspeciality-Oculoplasty
immunocompetent patients: treatment 17. Herbrecht R, Denning DW, Patterson TF, 21. Wakabayashi T, Oda H, Kinoshita N,
and outcome. Ophthalmology. Bennett JE, Greene RE, Oestmann JW, et Ogasawara A, Fujishiro Y, Kawanabe W.
2011;118(9):1886-1891. al ; Invasive Fungal Infections Group of Retrobulbar amphotericin B injections
the European Organisation for Research for treatment of invasive sino-orbital
13. Lam Choi VB, Yuen HK, Biswas J, Yanoff and Treatment of Cancer and the Global aspergillosis. Jpn J Ophthalmol. 2007 Jul-
M. Update in pathological diagnosis of Aspergillus Study Group. Voriconazole Aug;51(4):309-11.
orbital infections and inflammations. versus amphotericin B for primary
Middle East Afr J Ophthalmol therapy of invasive aspergillosis. N Engl Corresponding Author:
2011;18:268-76. J Med. 2002 Aug 8;347(6):408-15.
Dr. Gunjan Saluja MD, DNB
14. Agarwal E, Mulay K, Menon V, Sundar G, 18. Sivak-Callcott JA, Livesley N, Nugent Oculoplasty, Tumor & Pediatric
Honavar SG, Sharma M. Isolated Orbital RA, Rasmussen SL, Saeed P, Rootman Ophthalmology Services,
Aspergillosis in Immunocompetent J. Localized invasive sino-orbital Dr. R. P. Centre for Ophthalmic Sciences,
Patients: A Multicenter Study. Am J aspergillosis: characteristic features. Br J All India Institute of Medical Sciences,
Ophthalmol. 2016;165:125-132. Ophthalmol. 2004;88:681–687. New Delhi, India
15. King J, Henriet SSV, Warris A. 19. Levêque D, Nivoix Y, Jehl F, Herbrecht
Aspergillosis in Chronic Granulomatous R. Clinical pharmacokinetics of
Disease. J Fungi (Basel). 2016;2(2):15. voriconazole. Int J Antimicrob Agents.
2006 Apr;27(4):274-84.
16. Okuturlar Y, Ozkalemkas F, Ener B,
et al. Serum galactomannan levels in 20. Mainville N, Jordan DR. Orbital
the diagnosis of invasive aspergillosis. apergillosis treated with retrobulbar
Korean J Intern Med. 2015;30(6):899-905. amphotericin B. Orbit. 2012;31:15–7.
doi:10.3904/kjim.2015.30.6.899.
www.dosonline.org/dos-times DOS Times - Volume 26, Number 2, September-October 2020 89
Subspeciality-Oculoplasty
Tarsorrhaphy
Sahil Agrawal MD1, Saloni Gupta MS2, Neelam Pushker MD1
1Oculoplasty, Tumor & Pediatric Ophthalmology Services,
Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
2 Dept. Of Ophthalmology, Northern Railway Central Hospital, New Delhi, India
Tarsorrhaphy (blepharorrhaphy) is a Tarsorrhaphy are of the tape, cyanoacrylate glue, and injection
surgical fusion of the upper and lower botulinum toxin in levator muscle
eyelid margins.1,2 Bowman originally following types- (protective ptosis).5
described temporary paracentral
tarsorrhaphy that was modified by a) Complete or partial Tarsorrhaphy Except for nonsurgical temporary
Argyll Robertson and then by Panas. In - relying on whether or not all or closure, all the procedures require
1851, Mirault used it for the repair of solely a portion of the palpebral general or local anesthesia, depending
cicatricial ectropion to prevent pull on fissure is occluded. on the patient’s age. Local anesthesia
the lid.2 Since then, various techniques is administered by local infiltration
have been described for performing b) Lateral, medial, or paracentral of lids using injection 2% lidocaine
tarsorrhaphy, but the fundamental goal (median) – based on its location in (Xylocaine) with 1:100,000 dilution of
is to achieve adhesions between the the palpebral fissure. epinephrine.
upper and lower eyelid margins.
c) Temporary or permanent – Surgical Procedures:
How does tarsorrhaphy work? Temporary tarsorrhaphy stays
for a few days to weeks. It Temporary Tarsorrhaphy
The procedure reduces palpebral includes inter-marginal suture
aperture in patients with lagophthalmos tarsorrhaphy, Weeks tarsorrhaphy, Tarsorrhaphy is a sight-saving
due to facial palsy, exophthalmos, and glue tarsorrhaphy. Permanent procedure. Temporary tarsorrhaphy,
lid injuries, etc. It covers the cornea, procedures include Stamler and such as inter-marginal suture
thereby helping to heal exposure Tse lateral Tarsorrhaphy, Cole tarsorrhaphy and Weeks tarsorrhaphy,
keratopathy, corneal defect, and tarsorrhaphy, tarsal sliding flap are easy to perform, technically simple,
preventing further dryness of the ocular tarsorrhaphy, and posterior and straightforward procedures that
surface by reducing the exposed ocular lamellar tarsorrhaphy can be easily learned and attempted
surface area and preserving the tears. It even by a general ophthalmologist.
also immobilizes the eyelids, reducing The location, duration, and extent of It is usually done in patients with a
the wind-shield wiper effect on the tarsorrhaphy depend on the indication persistent epithelial defect, acute facial
cornea in patients with a persistent of the procedure. The surgical methods palsy, facial burns, or trauma, to prevent
corneal epithelial defect that permits are divided into temporary and exposure in proptosis and splint the lid
faster healing.3,4 It splints and stabilizes permanent procedures. The procedure in oculoplastic procedures.
the lid in patients with skin grafting has to be individualized depending
for cicatricial ectropion, traumatic on the need, keeping in mind the Inter-marginal Suture
laceration repair, burns, contracted importance of preserving the eyelid Tarsorrhaphy
socket reconstruction, etc. A partial margin structures that have both
tarsorrhaphy is usually preferred over functional and cosmetic functions. Various sutures used for inter-marginal
the total. It permits the instillation of Simple methods of tarsorrhaphy suture tarsorrhaphy are catgut, silk,
eye drops, allows patient to see, and are suture tarsorrhaphy, Weeks dacron, nylon, or polypropylene. A
assessment of the cornea can be done tarsorrhaphy, and amongst permanent double-armed 4-0 or 6-0 suture is passed
in patients with persistent epithelial techniques, where mobilization of through a rubber peg, then from the
defect or exposure keratopathy. posterior lamellae is not done. We need skin-muscle layer of the lower lid, 3-4
to understand that each procedure has mm from the ciliary margin to emerge
its indications and limitations. Some in the gray line. These sutures are then
nonsurgical methods also close the passed via the gray line of the upper lid
palpebral aperture, such as the use of
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Subspeciality-Oculoplasty
to emerge above the ciliary margin and Both needles of a double-armed 4-0 from liquid to solid employing anionic
finally passed through a rubber peg in braided silk suture threaded on a peg polymerization, initiated through small
a similar fashion and tied. The major are passed 3mm apart through the quantities of moisture. Utmost care has
disadvantage of this technique is that skin and muscle just below the ciliary to be taken during the procedure as
the sutures can loosen, get infected, or margin of the lower lid to come out in the glue is colorless and inadvertently
erode through the lid margin. Rubber the middle of the split margin. They are can enter the eye and lead to serious
pegs are unsightly, can loosen or fall continued through the opposite upper corneal problems as solidified glue has
off, and macerates the underlying skin.2 lid split margin to emerge just above the sharp edges. Also, it can lead to severe
For this reason, the use of pegs can be ciliary margin. The sutures are threaded adhesion of lids to the ocular surface.7
avoided (Figure 1). Suture tarsorrhaphy via another peg and tied securely to The duration of adhesion is also
stays for 10 – 20 days; thereafter the fetch the raw surfaces of the lids in close extremely variable, from a few hours
suture must be removed to prevent its apposition. The tarsorrhaphy sutures to days. Because of the limitations and
complications. must be left in place for ten days to risks, the procedure has not gained
witness complete healing (Figure 2).2 popularity.
Figure 1: Intermarginal suture The disadvantages of the procedure
tarsorrhaphy after reconstruction of are that immediately after suture Permanent Tarsorrhaphy
contracted socket. removal, the weak adhesion leads to lid Permanent tarsorrhaphy is indicated
Weeks Tarsorrhaphy separation and loss of effectivity of the in patients where we intend to keep
This technique was described by Weeks procedure in a few months. it for a longer duration or lifelong.
to create adhesion between upper and The procedure is more extensive and
lower lid margins by way of creating Figure 2: a) Schematic diagram showing involves splitting of the eyelid margin
a raw inter-marginal strip on the corresponding marginal epithelium areas into anterior and posterior lamellae
opposing surfaces of the lid margins. about 6-8 mm to be removed from both the and excising a horizontal strip of the
Emphasis was given to take care not to lids, respectively. b) A double-armed 6-0 silk sharp posterior border for permanent
cut the anterior and posterior borders suture is inserted over pegs and tied. and secure adhesion. Some procedures
of the lid margin. About 6 to 8mm Cyanoacrylate glue tarsorrhaphy also involve mobilization of posterior
areas are marked off with the point of a Schimek and Ballou in 1966, described lamellae to create flaps, leading to
knife at opposed sites of the upper and the use of acrylic adhesives to furnish more destruction of the lid margin. It
lower lid margins. A horizontal parallel a temporary adhesion of the lashes is important to remember that if one
incision is made to define the amount of of the upper eyelid to the skin of the plans to open the tarsorrhaphy in the
mucocutaneous inter-marginal tissue lower eyelid.6 Cyanoacrylate glue future, one should choose a procedure
to be excised. A clear rectangular raw is a mobile, clear, colorless liquid with minimal destruction of lid margin
area is created. The raw area is split adhesive. The monomer is changed anatomy. Disadvantages of permanent
into skin muscle and tarso-conjunctival tarsorrhaphy are esthetic appearance
lamellae to a depth of 2mm; this lets the and development of lid margin
wound spread and makes for a more deformities like marginal entropion, lid
excellent healing surface and more notch formation, lash misdirection and
robust adhesions.2 loss, etc. on opening it.
Lateral Tarsorrhaphy
Stamler and Tse in 1990 described a
tarsorrhaphy that did no longer require
bolster or nonabsorbable suture that
needs to be removed. The anterior and
posterior lamellae, of the lateral portion
of lids, are separated at the gray line by
passing a no. 11 Bard-Parker blade, 2 to
3mm deep along the anterior surface
of the tarsal plate.8,9 The mucous
membrane at the posterior lamellae
margin is grasped with a 0.3mm forceps
and excised horizontally with sharp
Westcott scissors to expose the edge of
the tarsal plate. After each of the tarsal
plates are exposed, a 5-0 polyglactin
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Subspeciality-Oculoplasty
suture on a spatulated needle is passed 5mm from the lateral canthal angle conjunctiva, till the lower border of
through the tarsal plates in a lamellar up to 10mm nasally. The extent of tarsus, to freely mobilize it up to fit in
fashion. The needle enters through closure is decided by pinching the the groove created in the upper lid. For
the anterior tarsal surface 3mm from temporal parts of the eyelids together making a groove of similar size in the
the edge and exits at the level of the while the patient tries to open his eyes. upper lid, the excision of the posterior
meibomian gland opening at the margin A temporally based triangular flap of lamella is done to fit the tongue of
of the posterior lamella. The suture lower lid tarsoconjunctiva is created. A the lower lid. 4-0 silk double-armed
must not be passed full thickness. The matching facet is fashioned in the upper suture is passed through the edge of
edges of the anterior lamellae are barely lid through resecting the corresponding the tarsoconjunctival tongue from
exerted with a 0.3mm forceps and closed triangular element of the upper lid without inwards. The sutures are then
with a running 7-0 polyglactin suture. tarsoconjunctiva. A double-armed 4-0 passed through the upper edge of the
The upper and lower tarsal plates heal black silk suture is passed through the upper lid groove from within outward
conjointly in 4 to 6 weeks, forming a lower lid flap from the conjunctival to come out on the skin surface. The
firm adhesion (Figure 3).8,9 surface, introduced through the upper tarsoconjunctival tongue is pulled into
lid defect and out onto the upper lid the upper lid groove, and the suture is
Exposed skin, and tied over a cotton bolster. The tied over a peg. A firm dressing is done
tarsoconjunctiva raw surfaces of the lower lid flap and to keep the tarsal tongue in place for the
the upper lid defect are juxtaposed for duration of healing.2 This procedure
Marginal an improved union. The suture is left in is usually indicated if repeated other
epithelium situ for two weeks (Figure 4). types of permanent tarsorrhaphies fail
removed (Figure 5).
Suture to pull anterior lamella
away from posterior lamella
after splitting at the gray line
Exposed tarsoconjunctiva
with marked inscion at
Upper lid
Figure 3: Stamlers and Tse lateral Figure 4: Coles permanent tarsorrhaphy a) Groove formed after
Tarsorrhaphy a) Splitting the anterior Split at the lid margin a line starting from tarsoconjunctival
and posterior lamella at the lateral 5-6mm the later canthal angle to 8-10mm nasally resection at upper lid
of the lid margin. b) Excising 1mm of the to a depth of 5mm. b) A temporally based
marginal epithelium (mucous membrane) triangular flap of lower lid tarsoconjunctiva Tongue from the
from the posterior lamella of both lids to is created corresponding to a matching facet lower
expose the tarsus c) Apposing the posterior fashioned in the upper lid by resecting the tarsoconjuctival
lamellae followed by anterior lamellae upper lid tarsoconjunctiva and apposing the dissection
using 5-0 polyglactin and 7-0 polyglactin, two using a double-armed 4-0 silk suture.
respectively. Figure 5: Sliding tarso-conjunctival
Tarsal sliding flap tarsorrhaphy tarsorrhaphy a) The upper and lower lids
Authors claim that this method In this approach, a sliding graft of are split into anterior and posterior lamella
preserves the integrity of the anterior tarsoconjunctiva is used in a ‘tongue at the gray line. A tarso-conjunctival
lamella, minimizing lid margin and groove’ manner. The lid margins groove is made in the upper lid to receive a
irregularity. The margins of the posterior are marked, and both lids are split at the tongue from the lower lid. b) The tongue of
lamella epithelialized normally without grayline. Two vertical cuts are given in tarsoconjunctiva is being drawn up to fill in
cosmetic and dysfunctional sequelae if the lateral lid, 5 – 6 mm apart in tarso- the groove of the upper lid using 4 -0 double-
the tarsorrhaphy is opened. armed silk suture.
Posterior Lamellar Tarsorrhaphy
Cole tarsorrhaphy Posterior lamellar tarsorrhaphy was
An excellent approach has been described in 1992 by Tanenbaum
described by Cole that permanently et al., as a tarsal pillar technique,
joins the lids, narrows the palpebral for narrowing and maintenance of
fissure, and leaves lashes intact.9 The the interpalpebral fissure in cases
adjoining upper and lower lateral lid
margins are separated to a depth of
92 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times
Subspeciality-Oculoplasty
Figure 6: Posterior lamellar in periorbital truama, 2 weeks post operative clinical picture. patching or tarsorrhaphy over complete
eyelid closure. Am J Ophthalmol
of exposure-related keratopathy of eyelid is then brought down in the 1987;103:339–40.
varied etiology, including facial nerve usual fashion as for a modified Hughes 4. Welch C, Baum J. Tarsorrhaphy
palsies, combined facial nerve palsy, flap and secured to the superior border for corneal disease in patients with
and trigeminal neuropathy with an of the lower eyelid posterior lamella rheumatoid arthritis. Ophthalmic Surg
aesthetic cornea, Graves’ disease, or vice versa using interrupted 6-0 1988;19:31–2.
congenital craniofacial anomalies, and polyglactin sutures with knots facing 5. Kaynak-Hekimhan P. Noncosmetic
severe keratitis sicca syndrome.10 away from sclera. In our experience, this periocular therapeutic applications
The tarsoconjunctival flap is fashioned is eye saving procedure in cases where of botulinum toxin. Middle East Afr
centrally after incising the gray line and the anterior lamella is severely deficient J Ophthalmol. 2010;17(2):113-120.
separating the anterior and posterior or unhealthy with poor chances of take doi:10.4103/0974-9233.63069
lamellae in the upper lid. The horizontal of skin graft as in acute burns or severe 6. Schimek RA, Ballou GS. Eastman 910
incision depends on the desired amount trauma with extensive anterior lamella monomer for plastic lit procedures. Am
of palpebral fissure closure. Two vertical tissue loss and also where repeated skin J Ophthalmol 1966; 62: 953-955.
incisions using number 15 blade and grafting or flap procedures fails because 7. Raynor LA. Treatment for inadvertent
Wescott scissors on either side of the of extensive periorbital scarring (Figure cyanoacrylate tarsorrhaphy. Arch
posterior lamella are given till the 6). Ophthalmol 1988; 106: 1033.
upper border of tarsus to obtain a freely 8. Stamler JF, Tse DT. A simple and
mobile transconjunctival flap. The References reliable technique for permanent lateral
lower eyelid is incised at the gray line 1. Rajak S, Rajak J, Selva D. Performing a tarsorrhaphy. Arch Ophthalmol 1990;
using a number 11 blade corresponding 108: 125-127. z
to the fashioned upper eyelid flap’s tarsorrhaphy. Community Eye Health. 9. Cole G. Lateral canthoplasty in
length. The epithelium from the 2015;28(89):10-11. ophthalmic plastic surgery. In Hughes
posterior lamellae margin’s surfaces 2. Fox SA. Basic techniques. In : Ophthalmic WL, editor : Ophthalmic Plastic Surgery,
are denuded. The flap from the upper plastic surgery. Grune and Stratton, Inc. American Academy of Ophthalmology
New York 1970; 73-103. 1961, 104-112.
3. Baum J. The advantages of partial 10. Tanenbaum M, Gossman MD, Bergin DJ,
Friedman HI, Lett D, Haines P, et al. The
tarsal pillar technique for narrowing
and maintenance of the interpalpebral
fissure. Ophthalmic Surg 1992;23:418-
25.
Corresponding Author:
Dr. Sahil Agrawal, MD
Oculoplasty, Tumor & Pediatric
Ophthalmology Services,
Dr. R. P. Centre for Ophthalmic Sciences,
All India Institute of Medical Sciences,
New Delhi, India
www.dosonline.org/dos-times DOS Times - Volume 26, Number 2, September-October 2020 93
Subspeciality-Oculoplasty
Botulinum Toxin- Therapeutic
Uses
Deepsekhar Das MD, Sujeeth Modaboyina MD, Neelam Pushker MD
Oculoplasty, Tumor & Pediatric Ophthalmology Services,
Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
Introduction is synthesized by the Clostridium of the terminal nerve cell surface
Botulinum toxin is an exotoxin bacterium as a single-chain polypeptide membrane.4 The toxin molecules
produced by an anaerobic gram-positive of w150 kDa.3 enters the vesicles by the process of
sporulating bacterium, Clostridium endocytosis.5 Once in the cytosol the
botulinum. It is also considered to be Mechanism of Action light chain acts as a zinc-dependant
the most potent biological toxin in The synaptic vesicles located in the endopeptidase that cleaves specific
nature.1 neural bouton contain acetylcholine SNARE proteins necessary for the
(ACh), which is required to initiate a exocytosis of acetylcholine molecules,
Types of Botulinum toxin muscle contraction. The fundamental thus attenuating neurotransmitter
Botulinum toxin exists as seven distinct principle of action of botulinum release.5
serotypes, designated from A to G, toxin is to inhibit the neuromuscular The clinically effect begins by 1-3 days
each with having a different terminal transmission by blocking the and the maximal paralytic effect is
binding configuration.2 Except for few, extracellular release of acetylcholine.4 reached by 4-7 days. In the subsequent
each strain of Clostridium produces After injection of botulinum toxin in the 2 months the axons expand, and new
only one type of toxin. Botulism in region of the target muscle, the heavy nerve terminal sprouts arise and reach
humans is caused by types A, B, E, F, and chain binds externally to gangliosides the muscle surface. The paralysis
potentially G. The neurotoxin molecule and protein acceptors on the bouton subsides by 2-4months.6
Therapeutic Indications Dose (Type Site Procedure
A Botuli-
Condition Clinical Features num toxin) Upper eyelid- pretarsal area The overacting periocular and facial
above the punctum and the muscles are marked, and small amount
Benign Involuntary and 12.5-25 U/ lateral canthus. of toxin is injected at each site. Eyelid
essential repetitive bilateral Lower eyelid- Pretarsal area injections are administered sub-cutane-
Blepharo- spasmodic contrac- eye below the punctum and the ously and brow injections are deeper.6,7,8
spasm (BEB)6 tion of the orbicularis lateral canthus. Each muscle requires different doses.
oculi muscle. Separate injection 1cm lateral Orbicularis Oculi- 1- 2.5U/injection,
Meige Syndrome: Bleph- to lateral canthus. maximum 5U
arospasm with dystonia Brow – 8 mm above the brow, Procerus- 2.5U/injection, maximum
of lower face. at the junction of medial and 2.5U
middle third and junction of Frontalis- 2.5U/injection, maximum
middle and lateral third. 10U
Corrugator-2.5U/injection, maximum
5U
94 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times
Subspeciality-Oculoplasty
Hemifacial Repetitive tonic con- Same as Addition to above sites- Zy- Bilateral injections have been advised
blepharo- tractions of unilateral above gomaticus major is injected for attaining a symmetrical smile.
spasm,7 facial muscles, usually under the prominence of
seen in middle age due zygoma.
to vascular compres- Levator labii Superioris
sion of seventh cranial alaeque nasi is targeted by
nerve root. injecting infero-medial to the
nasal labial fold.
Blephar- Non paralytic muscu- 10U/eye Mentalis muscle is injected if
ospasm lar abnormality with chin puckering is seen.
associated difficulty in starting lid
apraxia of elevation. Pre tarsal orbicularis oculi of
lid opening8 upper eyelid at four sites.
Orbicularis Young individual with 10U/eye
Myokymia involuntary contrac- Same as BEB Focal injections are administered at the
tion of a single fascicle affected sites
Eyelid re- of orbicularis oculi in
traction9 one or two eyelids. Inducing ptosis is the primary goal and therefore Botulinum Toxin
Usually seen in Thy- 2.5-5 U injection is injected in the Levator palpebrae superioris muscle using
roid eye disease. the following routes:
Transcutaneous: A half inch needle is passed supero-posteriorly in be-
Chemo-Tar- Performed in cases of 2.5-20U tween the eye and orbital roof at the mid pupillary plane and injection
sorrhaphy10 corneal compromise is administered.
to exposure secondary Transconjunctival approach: upper lid is everted using a Desmarre’s re-
to facial nerve palsy. tractor and injection is administered above the superior border of tarsus
In conditions with Advantages:
persistent epithelial Quick and easy OPD procedure avoiding surgery.
defects. Good option in active phase of thyroid eye disease when surgery cannot be done.11
Frey’s Syn- Post parotidectomy 40U First the perspiration is induced by feeding the subject a popsicle. The
drome ipsilateral facial perspi- affected area is cleaned and marked with the help of iodine tincture. In-
ration due to aberrant tradermal injections are administered at multiple sites over the affected
Lacrimal regeneration of facial area with each injection being separated by 1cm.
hypersecre- nerve secretomotor
tion11 salivary fibers with the After everting the eyelid with the help of a Desmarres retractor the
skin sweat glands. palpebral part of the lacrimal gland is visualized by asking the patient
to look down. Half is injected in the palpebral lobe while the rest is
- In patients with 5U injected in the orbital lobe.
Crocodile tears.
- Gustatory epiph-
ora.
- Primary lacrimal
gland hypersecre-
tion.
- Severely damaged
lacrimal drainage
system.
www.dosonline.org/dos-times DOS Times - Volume 26, Number 2, September-October 2020 95
Subspeciality-Oculoplasty
Spastic en- It results from ex- 5-10U Temporary relief can be achieved by weakening lower eyelid muscle
tropion12 cessive contraction tone with 5-10 U botulinum toxin injected into the pretarsal or pre-septal
of orbicularis oculi orbicularis muscle. This can counter the entropion for up to 3-4 months.
muscle.
Other indications include Nystagmus,13 Strabismus14
*Meige Syndrome require a higher total toxin dose and has a short spasm-free effect.
Reconstitution
In the manufacturing process, botulinum toxin
type A is mixed with sodium chloride and human
albumin is then added to prevent loss from surface
adsorption. Finally, the toxin is dried and stored
frozen. For use it must be reconstituted with saline
prior to injection, usually in concentrations of
1—2.5 U per 0.1ml.7
Complications
Ptosis Ptosis is one of the more frequent
complications and results from
passage of the toxin through the Figure 1. Image showing injection of periocular botulinum toxin for
orbital septum, either by diffusion Essential blepharospam.
or inadvertent placement. The in-
cidence has been reported as from
only a few percent to as much as
50%, with an average of 13.4%. The
duration of the ptosis tends to last
several weeks but is typically less
than the duration of the therapeutic
benefit on the orbicularis muscle.
Diplopia Diplopia is an uncommon compli-
cation and most commonly results
from inferior oblique muscle paral- Figure 2. Image showing injection of botulinum toxin subconjunctivally into
ysis. It can be associated with other levator palpebrae superioris muscle in upper eyelid lid retraction secondary to
muscles as well.7 Thyroid eye disease.
Ectropion/ Ectropion can result from weaken-
entropion ing of orbicularis muscle tone in
the face of a pre-existing horizontal
laxity of the lower eyelid support
structures, particularly the lateral
canthal tendon. This is an uncom-
mon side effect, with an overall
incidence of less than 1%.7
Keratitis, epiphora, dry eyes, lid edema, facial weak-
ness, lagophthalmos, ecchymosis, local pain, blurred
vision, and facial numbness.
Figure 3. Image showing injection of botulinum toxin into lacrimal gland.
96 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times
Subspeciality-Oculoplasty
Conclusion 6. Dutton JJ. Botulinum-A toxin in the 12. Steel DH, Hoh HB, Harrad RA, Collins
The use of botulinum toxin has changed treatment of craniocervical muscle CR. Botulinum toxin for the temporary
the management options of numerous spasms: short- and long-term, local and treatment of involutional lower lid
ophthalmic plastic conditions. In systemic effects. Surv Ophthalmol. 1996 entropion: a clinical and morphological
the present scenario it is an essential Jul-Aug;41(1):51-65. doi: 10.1016/s0039- study. Eye (Lond). 1997;11 ( Pt 4):472-
component which all ophthalmologists 6257(97)81995-9. PMID: 8827930. 5. doi: 10.1038/eye.1997.128. PMID:
should be well versed with. 9425409.
7. Dutton JJ, Fowler AM. Botulinum toxin
References in ophthalmology. Surv Ophthalmol. 13. Spielmann A. Nystagmus. Curr Opin
1. Adams GG, Kirkness CM, Lee JP. Ophthalmol. 1994 Oct;5(5):20-4. PMID:
2007 Jan-Feb;52(1):13-31. doi: 10.1016/j. 10150810.
Botulinum toxin A induced protective survophthal.2006.10.003. PMID:
ptosis. Eye (Lond). 1987;1 ( Pt 5):603- 17212988. 14. Campos EC, Schiavi C, Bellusci C. Critical
8. doi: 10.1038/eye.1987.93. PMID: age of botulinum toxin treatment in
3446541. 8. Forget R, Tozlovanu V, Iancu A, essential infantile esotropia. J Pediatr
Boghen D. Botulinum toxin improves Ophthalmol Strabismus. 2000 Nov-
2. Comella CL, Pullman SL. Botulinum lid opening delays in blepharospasm- Dec;37(6):328-32; quiz 354-5. PMID:
toxins in neurological disease. Muscle associated apraxia of lid opening. 11392405.
Nerve. 2004 May;29(5):628-44. doi: Neurology. 2002 Jun 25;58(12):1843-
10.1002/mus.20033. PMID: 15116366. 6. doi: 10.1212/wnl.58.12.1843. PMID: Corresponding Author:
12084888.
3. Dowell VR Jr. Botulism and Dr. Deepsekhar Das MD,
tetanus: selected epidemiologic and 9. Wabbels B. Botulinumtoxintherapie Oculoplasty, Tumor & Pediatric
microbiologic aspects. Rev Infect Dis. – neue Entwicklungen in der Ophthalmology Services,
1984 Mar-Apr;6 Suppl 1:S202-7. doi: Augenheilkunde[BotulinumToxin-New Dr. R. P. Centre for Ophthalmic Sciences,
10.1093/clinids/6.supplement_1.s202. Developments in Ophthalmology]. Klin All India Institute of Medical Sciences,
PMID: 6372030. Monbl Augenheilkd. 2018;235(6):721- New Delhi, India
724. doi:10.1055/s-0042-122339
4. Turton K, Chaddock JA, Acharya KR.
Botulinum and tetanus neurotoxins: 10. Ellis MF, Daniell M. An evaluation of the
structure, function and therapeutic safety and efficacy of botulinum toxin
utility. Trends Biochem Sci. 2002 type A (BOTOX) when used to produce a
Nov;27(11):552-8. doi: 10.1016/s0968- protective ptosis. Clin Exp Ophthalmol.
0004(02)02177-1. PMID: 12417130. 2001 Dec;29(6):394-9. doi: 10.1046/j.1442-
9071.2001.d01-28.x. PMID: 11778810.
5. Graham ME, Washbourne P, Wilson
MC, Burgoyne RD. Molecular analysis 11. Birch JF, Varma SK, Narula AA.
of SNAP-25 function in exocytosis. Ann Botulinum toxoid in the management
N Y Acad Sci. 2002 Oct;971:210-21. doi: of gustatory sweating (Frey's syndrome)
10.1111/j.1749-6632.2002.tb04465.x. after superficial parotidectomy. Br J Plast
PMID: 12438121. Surg. 1999 Apr;52(3):230-1. doi: 10.1054/
bjps.1998.3058. PMID: 10474477.
www.dosonline.org/dos-times DOS Times - Volume 26, Number 2, September-October 2020 97
Subspeciality-Oculoplasty
Oculoplasty basics: Clinical work
up proformas
Sujeeth Modaboyina, MD1, Sahil Agrawal, MD1, Neelam Pushker, MD1
Oculoplasty, Tumor & Pediatric Ophthalmology Services,
Dr. R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
Introduction along with basic workup proforma up proptosis, ptosis, contracted socket,
During clinical examination of patient helps in identifying the etiology, ectropion/entropion, and eyelid tumors.
before filling the following proforma localizing the pathology, and planning We would like to highlight staging,
complete ophthalmic examination the surgical approach. This chapter grading, and various examination steps
should be done. Filling the proforma will include proformas for working for working up the patients.
Proptosis work up
Inspection
1. Vision `
2. Facial asymmetry
3. Proptosis (Axial/ Abaxial )
4. Hertel’s exophthalmometry (Bar reading- )
5. Globe dystopia (mm) (horizontal/ vertical)
6. Lid fullness/ Skin changes/ Other
7. TED signs
8. Extraocular movements (Kestenbaum limbus test)
9. Conjunctival findings
10. Cornea
11. Pupillary reaction
12. Fundus examination – Choroidal folds / optic disc
13. Valsalva maneuver
Palpation
Location
Extent
Margins
Consistency
Tenderness
Pulsations/Thrill/Refill time
Compressibility
Temperature
Resistance to retropulsion
Bony margins
Lymph nodes
Auscultation (bruit)
Old photographs
Any other relevant findings
98 DOS Times - Volume 26, Number 2, September-October 2020 www.dosonline.org/dos-times
Subspeciality-Oculoplasty
Proptosis: Proptosis is defined as a exophthalmometer are very important Measurement of globe
forward (anterior) displacement of and must always be noted in case the dystopia: Horizontal dystopia is
globe in relation to skull- measured patient needs to be re-examined in the measured by the distance from the
by protrusion of the apex of the future. The patient is then told to open midline of bridge of the nose to the
cornea in front of outer orbital rim. their eyes and look straight ahead. The nasal limbus, compared bilaterally.
The term ‘exophthalmos’ is reserved examiner must align the red lines in -Vertical dystopia is measured by the
for globe protrusion secondary to the prisms by moving the head slightly superior or inferior deviation of the
endocrinological dysfunction1. laterally so that a single line is visible. central corneal reflex of the proptotic
Exophthalmometry: Exophthalmom- The tip of the corneal reflection, as eye from a horizontal line passing
etry (proptometry) measures in an an- seen in the prism and its corresponding through the centre of the normal
teroposterior plane, i.e., the distance value in millimeters, is noted. The eye. (Figure 3)
between the apex of the cornea and reading is usually the same in each eye
a bony point usually taken to be the and indicates the anterior distance from Limbus test of motility of
deepest portion of the lateral orbital the cornea to lateral orbital margins. Kestenbaum: This test is performed by
margin with the eye looking straight The normal values are in the range of holding a transparent millimeter ruler
ahead. Subjective assessment is done by 7-19mm, 7-21mm, 12-21mm, 12-20mm, horizontally in front of the cornea. In
worm’s eye view and Nafziger test. Ob- 12-24mm, and 12-23mm for Indian, measuring abduction, the location of
jective assessment is done by using Her- Caucasian, and African males and the nasal limbus point is noted on the
tel’s and Luedde’s exophthalmometer females, respectively2. (Figure 2) ruler in the primary position and in
Worm’s eye view: We will ask the maximum abduction. The difference
patient to tilt his head upwards, and we Figure 2: Hertel exophthalmometer immediately gives the degree of
will look from below to find protrusion Limitations: Readings are affected abduction in millimeters. Adduction
of the eyeball in relation to the other by poor fixation, depressed /fractured is measured similarly by determining
normal side. (Figure 1) lateral orbital rim, convergence error, the positions of the temporal limbus.
and head movements To measure elevation and depression,
Figure 1: Worms Eye View Luedde exophthalmometer: Luedde hold the ruler vertically. The examiner
Nafziger test: In Nafziger test, the exophthalmometer is a transparent should test each eye with his or her
examiner will stand behind the plastic millimeter ruler. The notch on own homonymous eye. Normal values
patient and will look from above the scale conforms to angle of the lateral established by Kestenbaum are 10
patient’s head. After bring upper and orbital rim, and scale readings are mm for adduction, abduction, and
lower orbital margins in the same from 0mm (end of the notch) to 40mm. depression, and 5 to 7mm for elevation.
plane, corneal visibility and its relative Parallax is minimized by using a scale
position compared to the other side will on both sides of the rod. Deep palpation: For palpation of
be assessed. orbital tumors beyond the orbital rim,
Hertel exophthalmometer: The the patient will look in the opposite
examiner must be at the same level as direction to the mass located, and the
that of the patient, and the right eye examiner presses his fingertip over the
must be kept closed while examining surface. After this patient looks in the
the right side and vice versa to reduce same direction of orbital mass (thereby
parallax error. With closed eyes, locate relaxing the septum), the examiner's
the orbital notch on the temporal side fingertip reaches beyond the orbital
of the orbit and place the concave rim for deeper palpation.
contact points. The bar readings of the
Figure 3: Measuremnt of vertical dystopia using millimeter scale
www.dosonline.org/dos-times DOS Times - Volume 26, Number 2, September-October 2020 99
Subspeciality-Oculoplasty
Ptosis Work up
Visual acuity
Facial asymmetry
Head posture
(Chin up position )
Frontalis over action
Cover test
Lid:
1. Lid fold (mm)
2. Lid Crease (mm)
3. Scar (previous surgery)
4. compensatory lid retraction/Pseudoptosis
Amount of ptosis (mm)
1. MRD1
2. MRD2
3. Palpebral fissure height
LPS excursion (mm)
Lagophthalmos (mm)
Lid lag
Bell’s phenomenon (grade)
MGJWP phenomenon (grade)
Extraocular movements (elevation deficit)
Corneal sensation
Tear film evaluation
1. TBUT
2. Schirmer’s test
Ocular surface
Pupil (size, reaction)
Refraction
Family album tomogram
Phenylephrine test/ additional tests (where needed)
Ptosis: Ptosis is defined as drooping ptosis is graded. (Figure 4 ) Mild: ≤2mm; Moderate: 3mm ; Severe:
of the upper eyelid lower than normal Figure 4: Ptosis measurement using ≥4mm
(1.5-2mm). millimeter scale. Ptosis can also be assessed using
torchlight. In this method position of the
Amount of ptosis: The amount of eyelid in relation to the pupillary border
ptosis can be measured by using a is assessed, with the patient looking at a
millimeter scale and asking the patient distant object and maintaining a stable
to focus at a distant object with the head position. Flash from torchlight
head properly supported3. The distance should not befall directly on the eyes of
between the relative position of center the patient; otherwise, it may give false
of the upper eyelid and central pupillary values because of reflex blepharospasm
reflex is measured, and the value is and pupillary constriction. Based on the
compared with the opposite normal position of the eyelid, ptosis is graded as:
eyelid. Based on the obtained value,
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