1040-5488/15/9209-0939/0 VOL. 92, NO. 9, PP.

939Y947
OPTOMETRY AND VISION SCIENCE
Copyright * 2015 American Academy of Optometry

REVIEW

Ophthalmic Procedures for Treatment of

Advanced Ocular Surface Diseases
Downloaded from https://journals.lww.com/optvissci by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3c9CHBlrWfCrdvrGGfZCc/DmQyLa5pdDqj7xIOPgnS+fiYauhpyR5bA== on 06/26/2018

Andrew H. Bartlett* and Jimmy D. Bartlett†

ABSTRACT
Dry eye disease and other ocular surface diseases are complex multifactorial disorders often characterized by ocular surface
inflammatory changes, instability of the tear film, and functional vision impairment. Recent research has led to new
concepts regarding diagnosis and management, and therapeutic interventions now include ocular lubricants, secreta-
gogues, topical and systemic anti-inflammatory and immunosuppressive agents, tear preservation, and, for advanced cases,
a variety of surgical approaches. This review considers contemporary procedures for treatment of advanced ocular surface
diseases, including thermal and electrocautery of the lacrimal puncta, lid surgeries such as tarsorrhaphy, and multiple
procedures to protect the exposed or compromised ocular surface.
(Optom Vis Sci 2015;92:939Y947)

Key Words: dry eye disease, ocular surface diseases, surgery, punctal cautery, tarsorrhaphy, gold weight, amniotic
membrane

D
ry eye disease (DED) is a multifactorial disease of the
tears and ocular surface that results in symptoms of
discomfort, visual disturbance, and tear film instability
with potential damage to the ocular surface. It is accompanied by
increased osmolarity of the tear film and inflammation of the
ocular surface.1
Patients with DED can present with mild, almost subclinical,
disease and, in other cases, can have marked signs and symptoms
accompanied by considerable ocular or visual morbidity and
impaired quality of life. Patients with the most advanced disease
can manifest severe and/or disabling and constant discomfort or
pain and constant and/or disabling visual symptoms. Marked
conjunctival staining and hyperemia, severe corneal epithelial
erosions, filamentary keratitis, or corneal ulceration frequently
occur. Keratinization or symblepharon and extremely low tear
break-up time or Schirmer test scores are common.1 It is for these
patients that surgical techniques have been developed to provide
ocular protection or to improve lacrimation or tear retention when
traditional pharmacologic interventions have failed.
This review addresses the epidemiology and significance of
DED, pathogenesis of the disease, and traditional therapeutic
*MD
†
OD, FAAO
Department of Ophthalmology, School of Medicine, Texas Tech University,
Lubbock, Texas (AHB); and Department of Optometry, School of Optometry,
The University of Alabama at Birmingham, Birmingham, Alabama (JDB).
options that are considered first-line management before surgery.
Modern surgical approaches and other procedures are described
for treatment of patients with the most severe and debilitating
clinical manifestations, including ocular surface disease states that
may exist alone or as comorbidities with DED.
EPIDEMIOLOGY AND SIGNIFICANCE
Large epidemiologic studies have suggested that the prevalence
of dry eye lies in the range of 5 to 30% of the population aged
50 years and older.2 It has been suggested that the true prevalence
of moderate to severe DED lies somewhere close to the lower
bound of the range.2 The large variation in observed prevalence
has been attributed to differences in the definition of disease used
and the methodologies used in the studies.3Y5 Among individuals
aged 50 years or older in the United States, it has been estimated
that approximately 3.2 million women and 1.7 million men have
moderate to severe dry eye.6,7
Symptoms associated with DED can include grittiness, foreign-
body sensation, discomfort, burning, and itching, and they are
often exacerbated by prolonged visual activity such as viewing
video display terminals. Dry eye disease can impact visual func-
tion,4 daily activities such as driving and reading,8 social and
physical well-being, and work place productivity. Chronic ocular
pain9,10 and the unremitting nature of DED can lead to despair or
depression and can potentially have a profound impact on overall
quality of life.4,5,11

Optometry and Vision Science, Vol. 92, No. 9, September 2015

Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.

940 Treatment of Advanced Ocular Surface DiseasesVBartlett and Bartlett
PATHOGENESIS
Dry eye disease was largely considered to be a tear volume
deficiency and tear film instability until Stern and colleagues12
proposed in 1998 the concept of lacrimal functional unit (LFU).
Components of the ocular surface (cornea, conjunctiva, accessory
lacrimal glands, and meibomian glands), the main lacrimal gland,
and corresponding sensory and motor innervation act as an in-
tegrated functional unit. When any component is compromised,
normal lacrimal support of the ocular surface can be impaired,
resulting in immune-based inflammation leading to lacrimal gland
and neural dysfunction.
Underlying conditions affecting the afferent component of the
LFU are common in patients with severe DED. The ocular surface
is extensively supplied by sensory and autonomic nerve fibers that
play a crucial role in maintaining healthy epithelial tissues. These
nerve fibers are altered by chronic inflammation in dry eye,
leading to a decrease in corneal sensitivity and a consequent
neurosecretory block that progressively reduces reflex tear secre-
tion.13 Trigeminal nerve trauma, familial dysautonomia, herpetic
keratitis, diabetes, and ablative refractive surgeries are com-
mon examples of conditions having a neurotrophic effect on the
cornea that leads to ocular surface desiccation. Severe neu-
rotrophic keratitis often requires surgical intervention. Disorders
of the glandular components of the LFU include trachoma, ocular
pemphigoid, Stevens-Johnson syndrome, chemical injury, graft-
versus-host disease (GVHD), Sjögren’s syndrome, and rosacea.14
The underlying pathogenesis of many dry eye types is driven
by tear hyperosmolarity and tear film instability. Tear hyper-
osmolarity causes damage to the surface epithelium by activating a
cascade of inflammatory events and the release of inflammatory
mediators into the tears and ocular surface tissues.13,15,16
TABLE 1.
Treatment recommendations by severity level
Level Key signs and symptoms
1 Mild or episodic discomfort
MGD variably present
Variable TBUT and Schirmer score
2 Moderate episodic or chronic discomfort
Variable conjunctival and corneal staining
MGD variably present
TBUT e10; Schirmer (mm/5 min) e10
3 Severe frequent or constant discomfort
Visual symptoms limit activity
Moderate to marked conjunctival and
corneal staining
Frequent MGD
TBUT e5; Schirmer (mm/5 min) e5
4 Severe or disabling discomfort or visual
symptoms
Marked to severe conjunctival staining and SPE
Filamentary keratitis, ulceration, trichiasis,
symblepharon
Immediate TBUT; Schirmer (mm/5 min) e2
Adapted from Management and Therapy Subcommittee of the International Dry Eye Workshop.24
MGD, meibomian gland dysfunction; TBUT, tear break-up time; SPE, superficial punctate erosions.
Optometry and Vision Science, Vol. 92, No. 9, September 2015
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
THERAPEUTIC MANAGEMENT
By far, the most widely used therapy of DED is tear replace-
ment by topical artificial tears and lubricating agents. These in-
clude traditional substituted cellulose ethers as well as newer
polymers and those that incorporate lipid-replacing moieties.17,18
Punctal occlusion using collagen- or silicone-based plugs to
minimize drainage of natural or artificial tears is the most com-
mon nonpharmacologic treatment. These and other traditional
therapies for DED are only palliative, however, because they re-
place or conserve the tears without modifying the underlying
disease process.19
During the last 15 years, topical anti-inflammatory and immu-
nomodulatory agents, such as steroids and cyclosporine, have been
widely used to target the underlying pathogenic mechanisms that
lead to the ocular surface damage associated with DED.20 Although
corticosteroids represent a mainstay in the management of many
patients, the severity of disease, presence of steroid side effects, or the
requirement for high doses of systemic steroids supports the ratio-
nale for immunosuppressive drugs such as antimetabolites, T-cell
inhibitors, and alkylating drugs.21 Treatment with these agents
can promote resolution of the acute inflammatory assault on the
lacrimal glands and bring improved control of signs and symptoms.
Systemic immunosuppressive agents may be particularly useful for
treatment of recalcitrant primary and secondary Sjögren’s syn-
drome22 and of chronic dry eye associated with GVHD.23
Regardless of the underlying etiology, disease severity is generally
considered the most important factor for treatment decision mak-
ing. Current recommendations are summarized in Table 1.24,25
Patients in level 4 who are refractory to conventional pharmacologic
and nonpharmacologic interventions may be candidates for addi-
tional procedures, including surgery.
Treatment
Education and environmental/dietary modifications
Tear substitutes
Eyelid therapy
All of the above, plus:
Anti-inflammatories
Tetracyclines for MGD, rosacea
Punctal plugs, secretagogues
Moisture chamber spectacles
All of the above, plus:
Autologous serum or plasma tears
Bandage contact lenses
Permanent punctal occlusion
All of the above, plus:
Systemic anti-inflammatory agents
Surgery (lid surgery, tarsorrhaphy; salivary gland, amniotic
membrane transplantation)
 Treatment of Advanced Ocular Surface DiseasesVBartlett and Bartlett
PROCEDURES TO PROMOTE TEAR RETENTION
The treatment of advanced DED may require surgical expertise
to improve symptoms as well as to prevent serious ocular sequelae
such as corneal perforation and scarring (Fig. 1). For this review,
we have divided advanced ocular surface disease patients into those
who are unresponsive to traditional medical treatment and con-
sequently require more effective forms of tear retention or en-
hancement and those where risk of corneal decompensation is
imminent and thus require aggressive ocular protection (Table 2).
The lid margin and its apposition to the globe play a vital role in
maintaining a well-lubricated ocular surface. This review does not
include the various pathologies, such as lid malpositions, com-
monly treated by oculoplastic specialists. These conditions must
be addressed before considering the procedures discussed here,
and often a multidisciplinary approach coordinating cornea and
oculoplastic specialties is needed for optimal treatment of certain
ocular surface disease states. Furthermore, it is vitally important
to accurately identify any underlying diagnosis such as GVHD,
autoimmune disease, chronic exposure or lid malposition, her-
petic keratitis, and other conditions whose pathophysiology may
continue to drive the ocular surface disease if left untreated.
Punctal Occlusion
Punctal occlusion with silicone plugs has long been an
established treatment for moderate to severe dry eye.26 Compli-
cations include conjunctival erosion, foreign-body sensation, and
long-term extrusion rates greater than 50% in some studies.27,28
Choosing an appropriately sized plug for the patient can improve
outcomes, but in patients who are dependent on permanent
punctal occlusion, high-temperature cautery is often an acceptable
option.29,30 After local subcutaneous anesthesia is given, high-
temperature disposable cautery devices or Hyfrecator electrocau-
tery probes (CONMED, Utica, NY) can be inserted into the
lacrimal punctum where heat or electric current is applied,
resulting in shrinkage and whitening of tissue around the cautery
tip.29 The cautery tip is then carefully removed, and the resul-
tant tissue destruction and scarring permanently close the lacri-
mal punctum. Dry eye symptoms, best-corrected visual acuity,
FIGURE 1.
A patient with advanced graft-versus-host disease (GVHD) from bone
marrow transplantation resulting in corneal perforation.
Optometry and Vision Science, Vol. 92, No. 9, September 2015
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
941
fluorescein and rose bengal staining, tear break-up time, and
Schirmer test values are typically significantly improved, and re-
canalization rates are exceedingly low.29 Patient selection is crucial
given the permanence of the procedure and potential for epiphora
in those patients where tear production overcomes the evaporative
component of dry eye. Thus, the surgeon’s judgment and expe-
rience are important in the decision to occlude or cauterize both
the upper and lower puncta.
An alternative to traditional punctal plugs has been described
using small injections of botulinum toxin (2.5 to 3.75 IU) to the
medial canthus.31,32 Paralysis of the orbicularis muscle impedes
the tear pump drainage pathway, reducing tear outflow and
leaving more tears to bathe the ocular surface. The technique
appears to be most accepted when applied to the lower eyelid
alone, as injecting both the upper and lower eyelid may lead to
patient complaints of cosmetically displeasing skin retractions and
excess weakness of the eyelids.31,32 Some studies32 have suggested
greater patient satisfaction and similar symptomatic improvement
compared with traditional punctal plug therapy. An obvious
pitfall of this treatment strategy is the need for repeated injections
because the local effect of the botulinum toxin is temporary. Given
the chronic nature of DED, this treatment approach may have
limited long-term value for patients with advanced disease.
Conjunctival Excision and Cautery
Conjunctivochalasis is defined as redundant folds of conjunctiva
typically located on the bulbar conjunctiva above the lower lid
margin. This change is typically associated with normal aging and is
consequently often overlooked as a component of dry eye symp-
toms.33 The condition is typically differentiated from the boggy
conjunctiva seen in allergic conjunctivitis by the classic inferior
location of the former as well as by its failure to respond to topical
antihistamine/mast cell stabilizer therapy.34 Several authors33Y35
have suggested that conjunctivochalasis impacts tear film dynamics,
contributing to dry eye symptoms in its early stages, potentially
disrupting tear outflow in moderate stages, and even causing ocular
surface exposure in advanced stages. Affected patients often report
ocular dryness, pain, hyperemia, blurred vision, and epiphora.36
Severe cases have been linked to increased tear osmolarity and in-
flammatory markers, which are often associated with dry eye
states.37,38 Le and colleagues39 have recently demonstrated that
patients with conjunctivochalasis have significantly decreased tear
film stability even compared with those with DED and have sig-
nificantly higher Ocular Surface Disease Index (OSDI) scores than
do normal controls.
Depending on the frequency and severity of symptoms, a number
of surgical procedures have been proposed. For cases of epiphora
associated with mechanical obstruction of the lacrimal puncta by
redundant conjunctiva, conjunctival excision can be performed with
satisfactory improvement in symptoms.40 Good results have been
described with and without amniotic membrane transplantation.33
Considering the weakened adherence of conjunctiva to under-
lying sclera with age, one may be able to restore the original anatomic
configuration by increasing tissue adhesion. A less invasive approach
has been proposed using electrocauterization to tack the bulbar
conjunctiva back to the underlying sclera.41,42 Conjunctival cautery
can alleviate symptoms when conventional medical therapies for
942 Treatment of Advanced Ocular Surface DiseasesVBartlett and Bartlett

DED have failed.41 This less invasive approach is also favorable as it
leaves the option of conjunctival excision for future consideration
should symptoms still be significant and unresponsive to the initial
procedure. Some surgeons43 have had good results combining
surgical excision with cautery.
Meibomian Gland Expression
New procedures aimed to treat the meibomian glands
have recently been proposed.44Y48 The U.S. Food and Drug
AdministrationYapproved LipiFlow Thermal Pulsation System
(TearScience, Morrisville, NC) was developed to aid expression of
the meibomian gland orifices. This device works by clamping the
anterior and posterior lamellar surfaces of the upper and lower
lids and simultaneously using gentle heat and small pulsations to
help drive stagnant meibomian secretions from their ducts and
out of the orifices. Adverse events associated with the procedure
include moderate resolving conjunctival injection, small pete-
chial hemorrhages on the eyelid and/or conjunctiva that resolved
without treatment, and minimal increase in corneal staining scores

TABLE 2.
Procedures for treatment of advanced ocular surface diseases

Procedure Indications Complications

Tear retention/enhancement
Silicone punctal plugs Moderate to severe dry eye unresponsive to Conjunctival erosion, foreign-body sensation,
traditional artificial tear supplementation long-term extrusion rates 950%
Punctal cautery Moderate to severe dry eye where traditional Permanence of procedure and
punctal plugs have failed or are poorly tolerated small risk of recanalization
Botulinum toxin Moderate to severe dry eye unresponsive to Cosmetically displeasing skin retractions and
to medial canthus traditional artificial tear supplementation excess weakness of eyelids (if upper and lower
lids injected), need for repeat injections
Conjunctival Persistent dry eye symptoms with Conjunctival scarring
excision/cautery conjunctivochalasis causing mechanical
tear film instability or outflow
obstruction
LipiFlow Symptomatic MGD, meibomian gland Conjunctival injection, small petechial hemorrhages
inspissation not responding to lid scrubs on eyelid and/or conjunctiva, increase in corneal
and warm compresses staining immediately after treatment
Meibomian probing Symptomatic MGD, meibomian gland Ductal and subconjunctival hemorrhage
inspissation not responding to lid scrubs with discomfort, need for reprobing for
and warm compresses recurrent symptoms
Autologous gland Severe dry eye unresponsive to traditional Epiphora, which may be worsened with exercise/hot
transplantation medical management environments; host site numbness; recipient site
necrosis; transplantation failure; herpes simplex
keratitis; entropion
Ocular exposure and neurotrophic cornea
Tarsorrhaphy Neurotrophic ulcers, exposure keratopathy, Cosmesis, trichiasis, adhesion between upper
postYpenetrating keratoplasty, severe dry and lower lids after tarsorrhaphy lysis,
eye syndrome, radiation keratopathy, premature opening of tarsorrhaphy,
ocular cicatricial pemphigoid, Stevens-Johnson pyogenic granuloma, eyelid keloid formation
syndrome
Gold weight placement Chronic exposure from thyroid eye disease, cranial Astigmatism, cosmetic bulge of the implant,
nerve VII palsy (non-Bell’s), other conditions ptosis, migration, extrusion
with chronic corneal exposure unresponsive to
lubrication with artificial tears and ointments
Botulinum toxin to Bell’s palsy with corneal exposure that is Superior rectus underaction, diplopia,
levator expected to recover across time nonhealing epithelial defects, prolonged ptosis
Conjunctival flap Severe ocular surface disease with poor Cosmesis, poor vision
visual potential
Prokera, AmbioDisk, Stevens-Johnson syndrome, thermal and chemical Intolerance, expense, inventory issues
amniotic membrane ocular surface burns, severe bacterial keratitis
transplant with persistent epithelial defect, postsurgical
(e.g., pterygium) or other persistent corneal or
conjunctival epithelial defect
Gas-permeable scleral Stevens-Johnson syndrome, ocular cicatricial Contact lens intolerance, microbial keratitis
contact lenses pemphigoid, exposure keratitis,
neurotrophic keratitis, Sjögren’s syndrome,
persistent epithelial defects
MGD, meibomian gland dysfunction.

Optometry and Vision Science, Vol. 92, No. 9, September 2015

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 Treatment of Advanced Ocular Surface DiseasesVBartlett and Bartlett
FIGURE 2.
Lid margin hemorrhages resulting from meibomian gland probing (reprinted
with permission from Wladis48).
immediately after treatment (without epithelial defects) that re-
solved spontaneously at 1 day posttreatment.44 Early studies have
generally demonstrated improvement in signs and symptoms in-
cluding OSDI scores and meibomian gland secretion scores for up to
12 months after a single 12-min treatment.44,49 When compared
during a 3-month treatment interval, a single LipiFlow treatment
may be at least as effective as twice-daily eyelid warming and massage
performed manually by the patient.50 Symptomatic improvement
appears to be better in patients with less severe meibomian gland
atrophy compared with patients who have more dropout preceding
treatment.51
Intraductal probing has also been proposed using small probes to
mechanically open and dilate congested meibomian gland orifices.47
At the slit lamp, after topical or local subcutaneous anesthesia, a
stainless steel 2-mm probe and subsequently larger 4-mm probe are
used to penetrate the meibomian orifice, adjusting the angle of
FIGURE 3.
Lateral tarsorrhaphy for treatment of excessive corneal exposure.
Optometry and Vision Science, Vol. 92, No. 9, September 2015
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943
FIGURE 4.
Gold weight placement. A. Intraoperative suturing of weight between tarsus
and orbicularis for treatment of paralytic lagophthalmos. B. Patient with
implanted gold weight for lagophthalmos secondary to traumatic seventh
cranial nerve palsy demonstrating slight cosmetic bulge and ptosis.
insertion to ensure smooth passage of the probe. This technique has
also been described with the use of a hyfrecator tip without the
optional electrical current applied. In limited case series, intraductal
probing has been reported to relieve symptoms and improve
meibomian secretion quality but is not without risk.47,48 Ductal and
subconjunctival hemorrhage (Fig. 2) with discomfort have been
reported, and the need to reprobe for recurrence of symptoms
in certain patients is well documented.47 Benefits include im-
provement in OSDI scores, less reliance on doxycycline, and, in
many cases, lasting relief of symptoms with less long-term artificial
tear usage.48
Autologous Gland Transplantation
For eyes that are still unresponsive to treatment methods discussed
above and where preservation of the ocular surface is at risk, methods
of autologous nonocular gland transplantation have been described.52Y56
Autologous transplantation of the submandibular gland has been
proposed in cases of DED that are not responsive to traditional
medical management.52 Although the ocular tear film is complex
and unique, the mucinous composition of major and minor salivary
glands approaches the relative osmolality and protein content of
tears.53,55,56 The procedure is to transfer the submandibular gland to
the temporal fossa posterior to the frontal branch of the facial nerve.
The secretory duct is passed subcutaneously to its distal end at the
temporal edge of the upper lid tarsus. Innervation of the graft re-
mains absent, but its vascular perfusion is felt to play a primary role
in regulating the quantity of secretion.55 Variations of this technique
944 Treatment of Advanced Ocular Surface DiseasesVBartlett and Bartlett
have been described using portions of the submandibular gland as
well as minor salivary glands of the buccal, labial, and palatal mu-
cosa.53 In the limited long-term studies that have been performed,
approximately half of patients reported subjective improvement
when judged against the complexity and burden of the surgical
procedures and follow-up.57 Benefits include reduced reliance on
artificial tear substitutes, improved corneal fluorescein staining, and
improved visual acuity.55,56
Given the extensive list of complications, autologous gland
transplantation has been used at only a few select centers and has
not become a standard technique in the United States even for
severe cases of dry eye.57 This procedure has been documented
to cause extensive epiphora in approximately half of patients
6 months postoperatively.58 The salivary gland secretions remain
in a ‘‘saliva-tear’’ composition given the source gland properties,
and epiphora can become worse with exercise and in hot envi-
ronments.57 Some cases require partial graft excision/revision with
a second procedure to mediate symptoms of epiphora. Along with
the risk of host site numbness, recipient site necrosis, and trans-
plantation failure, additional reports of herpetic keratitis, ptosis,
and entropion limit widespread use of this technique.53,54 The
procedure also requires a multidisciplinary approach with oto-
rhinolaryngology, oral maxillofacial, and ophthalmologic con-
sultation, which can be difficult to coordinate.
PROCEDURES TO PROMOTE
OCULAR PROTECTION
The ocular surface, lacrimal glands, and sensory and autonomic
nerve fibers express a number of cytokines, neuropeptides, and
neuromediators that are critical in maintaining an intact LFU, as
described earlier. When one or more of these components are
diseased or missing, the cornea and external ocular surface is at risk
of tissue breakdown, which often presents as a neurotrophic ulcer
or even perforation.59 In these instances, more invasive surgical
approaches are often indicated. The tarsorrhaphy (Fig. 3) has
long been used to temporarily or permanently improve coverage
for an exposed ocular surface. The list of indications is extensive
and includes neurotrophic ulcers, exposure keratopathy from a
number of conditions, postsurgical states including penetrating
keratoplasty, dry eye syndrome, radiation keratopathy, ocular
cicatricial pemphigoid, and Stevens-Johnson syndrome.60 Several
techniques have been described using various suture materials and
even cyanoacrylate glue.61 Benefits are well established and in-
clude the main goal of restoring an intact corneal epithelium.62
Complications are typically limited and minor relative to the
original condition and include trichiasis, adhesion between upper
and lower lids after tarsorrhaphy lysis, premature opening of the
tarsorrhaphy, pyogenic granuloma, keloid formation of the eyelid,
and unacceptable cosmesis.60 There is an alternative, however, for
a certain subset of patients.
For patients with chronic exposure because of thyroid eye
disease, seventh cranial nerve palsy, or other conditions where
chronic corneal exposure is leading to stromal thinning or epi-
thelial breakdown not responsive to aggressive artificial tears and
ointments, gold or platinum weight implants can be used to aid
closure of the affected lid. This technique involves surgically
implanting a flat gold or platinum weight of known mass between
Optometry and Vision Science, Vol. 92, No. 9, September 2015
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the tarsal plate and anterior orbicularis and skin (Fig. 4). Multiple
weight sizes are available that help tailor the procedure for the
precise amount of corneal exposure to be treated. Particularly
useful in seventh cranial nerve palsy, this additional weight allows
for complete closure of the eyelids while preserving the ability to
open the eye via the unaffected levator palpebrae superioris, which
is controlled by the functional third cranial nerve, and Mueller’s
muscle, which is controlled by the sympathetic division of the
autonomic nervous system. Complications include induced astig-
matism, cosmetic bulge of the implant, ptosis, implant migration,
and extrusion.63
Some patients with exposure that is expected to recover with
time, such as those with a recent Bell’s palsy, may benefit from
botulinum toxin A injected into the levator palpebrae superioris.
Widely used in the ophthalmic field to treat hemifacial spasm
as well as blepharospasm, botulinum toxin has been described
in patients with exposure caused by cranial nerve (V or VII) palsy
as a temporizing measure before the use of tarsorrhaphy or other
more extensive procedures.64Y66 On average, ptosis is induced for
12 weeks but can be variable.64 Patient selection is critical because
patients with corneal erosions tend to do better than those with
sterile ulcers with respect to epithelial healing. Patients younger
than 50 years also tend to fare better than older patients and are
less likely to go on to need tarsorrhaphy or other more perma-
nent or disfiguring procedures.64 In patients who fail to respond,
tarsorrhaphy is often ultimately needed, but botulinum injec-
tion is useful as a less invasive alternative for patients who are good
candidates. Potential complications include superior rectus
underaction, diplopia, nonhealing epithelial defects (treatment
failure), and prolonged ptosis.64,66 Some clinicians have modified
the technique and location of injection to prevent superior rectus
toxicity by using a transconjunctival rather than traditional trans-
cutaneous approach.67
When significant pathology results in dryness that progresses
to a neurotrophic cornea, microsurgical procedures are often
needed to maintain integrity of not only the ocular surface but also
the eye itself. Conjunctival flaps have been performed for more
than 100 years for eyes with poor visual potential where the ocular
surface is severely compromised.68,69 It has been theorized that the
nutrients and structural support provided by the conjunctival flap
can aid in recovery of the host tissue.68 The technique involves
mobilizing the conjunctiva around the limbus and suturing the
free conjunctiva across the cornea so that adequate coverage is
achieved.68 Conjunctival flaps are sometimes necessary to aid
healing and to allow time for reepithelialization of the diseased
ocular surface. The classic Gunderson-style flap was traditionally
designed to be left in place permanently, covering the entire
cornea from limbus to limbus. Variations of this technique using a
segmental flap have been used in recent years for eyes with good
visual potential to aid healing of a section of the cornea. After
healing, which may require months, the flap is taken down to
restore functional vision.68 While the flap is in place, vision is
frequently severely limited and cosmesis can be a concern, but
often there are few other options for these patients.59
When healthy conjunctiva is unavailable to perform a flap, or
depending on surgeon preference and experience, amniotic membranes
have been used in recent years with good results. In addition to the
structural support and coverage of areas of epithelial breakdown,
 Treatment of Advanced Ocular Surface DiseasesVBartlett and Bartlett
amniotic membranes may also prevent ocular surface inflammation
and vascularization, promote epithelial healing, and are even reported
to have antibacterial properties.59,70,71 The procedure involves su-
turing single or multiple cryopreserved amniotic membrane(s) in
place over the area of concern.72 This material has also been
sandwiched between two polycarbonate donut-shaped rings (similar
to a symblepharon ring) and manufactured under the brand name
Prokera (Bio-Tissue, Inc., Miami, FL) to provide a sutureless option
for patients. AmbioDisk (IOP Ophthalmics, Costa Mesa, CA) is a
processed, dehydrated, sterilized human amniotic membrane allograft
that is placed dry on the corneal surface and secured with sutures,
tissue adhesives, or with a contact lens overlay.73 These devices are
intended to treat severe ocular surface disease such as Stevens-Johnson
syndrome as well as thermal and chemical burns, neurotrophic ker-
atitis, severe bacterial keratitis with persistent epithelial defect, and
other conditions where preserving remaining limbal stem cell integrity
is crucial.74 Amniotic membranes are often expensive, and their in-
frequent use may present logistical issues with on-site inventory.
Gas-permeable scleral contact lenses can provide an additional
effective strategy in the therapeutic management and visual re-
habilitation of patients with severe ocular surface disease.75Y79
This approach has been used for managing many ocular surface
disorders refractory to other treatment measures or otherwise
requiring keratoplasty, including Stevens-Johnson syndrome,
ocular cicatricial pemphigoid, exposure keratitis, neurotrophic
keratitis, and Sjögren’s syndrome.75 Scleral lenses can promote
healing of persistent epithelial defects that failed to heal after other
therapeutic measures. Reepithelialization appears to be supported
by a combination of oxygenation, moisture, and protection of the
fragile surface epithelium afforded by the scleral lens.80,81 In
addition to providing visual enhancement, this treatment mo-
dality may further improve quality of life by significantly reducing
photophobia and ocular discomfort.75,81 Complications include
contact lens intolerance76 and microbial keratitis.80,81
In the United States, approximately 5 million men and women
have moderate to severe DED,6,7 and many of these patients and
others with problematic ocular surface abnormalities fail to re-
spond to traditional medical therapies. Fortunately, ophthalmic
procedures are available to promote tear retention or to provide
ocular protection for patients with the most advanced disease
states. Judicious selection of the appropriate procedure(s) may not
only enhance the patient’s visual potential but also improve the
patient’s overall quality of life.
ACKNOWLEDGMENTS
The authors have no financial or commercial interest in the products and
procedures discussed in this article.
Received January 27, 2015; accepted April 3, 2015.
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Jimmy D. Bartlett
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