CORNEA 5th Ed-804-821
CORNEA 5th Ed-804-821
KEY CONCEPTS
• K eratoconus should be suspected in a young person whose eyes • D eep anterior lamellar keratoplasty is appropriate for the
cannot be refracted to 20/20 or requires multiple changes of keratoconus patient without deep stromal scarring and
glasses. has the advantage of eliminating the risk of endothelial
• Atopy, Ehlers-Danlos syndrome, Down syndrome, Leber rejection. Stromal rejection, however, can occasionally be
congenital amaurosis, and eye rubbing are associated with problematic.
keratoconus. • The hallmark of pellucid marginal degeneration (PMD) is corneal
• Thinning at the apex of corneal protrusion is the hallmark of protrusion central to a peripheral band of corneal thinning,
keratoconus. which typically occurs inferiorly. The crab-claw pattern on a
• Inferior steepening, superior flattening, skewing of the radial axes, power map is often seen in PMD but can also be seen in inferior
decentered corneal thinning, and islands of anterior and posterior keratoconus.
elevation are all corneal topographic and tomographic findings • In keratoglobus, the cornea is diffusely steep and thin with
consistent with keratoconus. maximum thinning in the periphery. In contrast to congenital
• Cornea crosslinking to reduce keratoconus progression works best glaucoma and anterior megalophthalmos, the corneal diameter is
in young patients with mild to moderate disease. only slightly enlarged.
The noninflammatory ectatic diseases of the cornea discussed in this When the above treatments fail to achieve adequate visual function,
chapter are keratoconus, pellucid marginal degeneration (PMD), kera- either deep anterior lamellar keratoplasty (DALK) or penetrating kera-
toglobus, and posterior keratoconus. Beside the similarities in name, toplasty (PKP) has the potential to restore vision.
these conditions, to varying degrees, are similar in clinical presentation Posterior keratoconus differs from the other noninflammatory
(Table 73.1). Corneal ectasia following keratorefractive surgery resem- ectatic disorders in many respects. To reduce the confusion caused by
bles keratoconus and is presumed to be iatrogenic in nature and will the similarity in name, it is included in the discussion that follows.
also be discussed in this chapter.
Corneal thinning is a hallmark of these ectatic diseases. Recogniz- KERATOCONUS
ing the relationship between the points of maximal thinning and max-
imal corneal protrusion is helpful in differentiating these conditions. Definition
Distortion of the anterior corneal curvature occurs in keratoconus, Keratoconus is a condition in which the cornea assumes a conical
PMD, and keratoglobus (Fig. 73.1) and results in varying degrees of shape because of thinning and protrusion. The process is convention-
reduced visual function. ally thought to be noninflammatory. Cellular infiltration and vascu-
Corneal topography and corneal tomography have dramatically larization do not occur. It is usually bilateral, although it may present
improved the sensitivity of detection of these ectatic disorders, partic- with marked asymmetry. The disease typically involves the central
ularly in the case of keratoconus. This has prompted debate on appro- two-thirds of the cornea with the apex of the cone usually centered
priate terminology for the patient with diagnostic evidence of inferior just below the visual axis. This condition may result in mild to marked
steepening, islands of elevation, or eccentric thinning, but without visual impairment.
overt clinical signs or symptoms of keratoconus. Keratoconus suspect
and subclinical keratoconus are commonly used terms. Forme fruste Prevalence, Distribution, and Course
keratoconus refers to disease in which progression appears to have been Keratoconus occurs in people of all races with no significant gender
arrested at an early stage. Topography and tomography have been of predominance.
great value in refining study populations for genetic studies and are an Reported prevalence of keratoconus varies widely depending on
integral part of the screening examination for keratorefractive surgery. diagnostic criteria and geographic location, ranging from 0.3 to 2300
Keratoconus, PMD, and keratoglobus share a basic treatment algo- per 100,000.1 Studies in Asia2 and the Middle East3 suggest higher
rithm early in the course of disease. Visual correction begins with rates of keratoconus in these regions compared with reported rates in
glasses; when unsatisfactory this is followed by contact lens fitting. Caucasians.
Patients with mild to moderate keratoconus may benefit from corneal Keratoconus usually occurs bilaterally. While some experts believe
collagen crosslinking (CXL) to help limit progression. Intrastromal that true unilateral keratoconus does not exist,4 cases of unilateral
ring insertion may improve contact lens tolerance and visual function. keratoconus have been reported.5 Asymmetry in keratoconus may be
749
750 PART VII Diseases of the Cornea
$ % & '
Fig. 73.1 The presence of corneal thinning and the type of contour abnormality can be helpful in recognizing
the type of ectatic disorder. (A) Keratoconus; (B) pellucid marginal degeneration; (C) keratoglobus; and (D)
posterior keratoconus.
related to eye rubbing.6 It has been convincingly shown that contem- Keratoconus also occurs with increased frequency among develop-
porary diagnostic analysis results in the detection of subclinical kera- mentally delayed individuals without Down syndrome, and the inci-
toconus in the fellow eye. With this in mind, the incidence of unilateral dence of unilateral disease may be substantially higher in this group
involvement is probably in the range of 2%–4%. compared with the general population.17
The onset of keratoconus occurs at about the age of puberty. The Two plausible explanations for this association with keratoconus
cornea begins to thin and protrude, resulting in irregular astigmatism are that either genetic abnormalities underlie structural or biochem-
with what is usually a steep curvature. The rate of progression is more ical changes resulting in the well-recognized phenotype or that eye
rapid in the teens and 20s, slows in the 30s, and typically stops in the rubbing is the root cause. Corneal hydrops occurs with increased fre-
early 40s. For this reason, younger patients should be examined more quency in patients with Down syndrome or other forms of intellec-
frequently. If a faint broad iron ring is present early on in the course, it tual impairment, and this may also result from habitual oculodigital
becomes a thinner, more discrete ring over time. stimulation.
Progression has been defined as a consistent change in at least 3 of Keratoconus has long been known to occur in patients with nonin-
the following parameters: (1) steepening of the anterior corneal sur- flammatory connective tissue disorders.15 Most notable among these
face, (2) steepening of the posterior corneal surface, or (3) thinning are Ehlers−Danlos syndrome and osteogenesis imperfecta. Robertson
and/or an increase in the rate of corneal thickness change from the found the prevalence of hypermobility of the joints to be 50% in 44
periphery to the thinnest point.4 consecutive keratoconus patients.18 Joint hypermobility in keratoconus
has subsequently been confirmed, especially for the metacarpophalan-
geal and wrist joints.19
Associated Disease An increased prevalence (6%–58%)20–22 of mitral valve prolapse
Systemic Disease has been found in keratoconus patients. The prevalence appears to
Over the past half century, much has been written linking keratoconus increase with severity of the corneal disease. In contrast, Street et al.23
to atopic diseases.7–9 were unable to confirm the association of keratoconus, mitral valve
The Dundee University Scottish Keratoconus Study10 (DUSK) prolapse, and joint hypermobility in a well-controlled study of 95 ker-
reviewed 200 keratoconus subjects and found the incidence of hay atoconus patients. The association with floppy eyelid syndrome has
fever to be 30%, asthma 23%, eczema 14%; comparative survey results been reported with a prevalence of 17%.24 Given the well-established
of 100 control patients showed that incidence of these disorders was association between floppy eyelid syndrome and sleep apnea, it is not
16%, 6%, and 16%, respectively. The Collaborative Longitudinal Evalu- surprising that a higher proportion of keratoconus patients was found
ation of Keratoconus (CLEK) study11 of over 1200 keratoconus patients to either suffer from or were at risk of sleep apnea in a study based on
found a 53% incidence of atopic disease. The diagnosis of keratoconus the Berlin Questionnaire.25
in this study was made prior to the advent of tomography. In two large case-control studies,26,27 the prevalence of diabe-
A thorough evaluation of the keratoconus patient should include a tes was significantly lower in keratoconus patients versus a control
complete history of atopic disease. Appropriate referrals can be made if group. Statistical analysis demonstrated a strong protective effect
significant atopic disease is newly revealed. Allergic lid and conjuncti- of diabetes against keratoconus. This effect was only seen in type
val disease can adversely affect contact lens tolerance. As a result, sur- 2 diabetes.
gical intervention may be required earlier in the course of the disease. Mannis et al.28 found patients with keratoconus and other chronic
The association with Down syndrome has been strongly estab- eye diseases to be less conforming and more passive-aggressive, para-
lished12–14 with the prevalence of keratoconus estimated to be 10- to noid, and hypomanic than normal control individuals based on per-
300-fold higher than the general population.15,16 sonality testing.
CHAPTER 73 Noninflammatory Ectatic Disorders 751
Additional associations between keratoconus and systemic diseases As a result of this study, a genetic basis, rather than an environmental
can be found in Table 73.2. cause such as eye rubbing, was suspected.
Additional associations between keratoconus and ocular diseases
Ocular Disease appear in Table 73.2.
Keratoconus may appear in association with other ocular conditions.
A classic example is retinitis pigmentosa.29 Leber congenital amaurosis Etiology
is frequently complicated by keratoconus and cataract. In a classic large The various associations with systemic and ocular diseases have led
study,30 more than one-third of Leber patients over 45 years old also to the development of many theories regarding the etiology of kera-
had keratoconus. Keratoconus occurring in patients with advancing toconus. Nevertheless, the cause of this corneal disorder remains an
age has been confirmed.31 Moschos et al.32 studied 233 keratoconus enigma.34 The current consensus is that the pathophysiology of kerato-
patients and found 2.6% with electroretinogram abnormalities and conus is multifactorial and influenced by environmental, genetic, and
3.9% with abnormal visual evoked response, confirming the presence biochemical factors.4 The etiology of keratoconus is considered below
of diffuse or central tapetoretinal degeneration. Elder33 found a much and in the three sections that follow.
higher incidence of keratoconus among children with Leber congenital Several reports have implicated eye rubbing as an important etio-
amaurosis compared with a group of children blind from other causes. logic factor in the development of keratoconus.6,35 In the DUSK study10
752 PART VII Diseases of the Cornea
of 200 keratoconus patients, 48% reported frequent eye rubbing, while corneal topography. In addition, evaluations may have been performed
only 11% reported never rubbing their eyes. in younger patients, prior to the development of keratoconus. At least
The microtrauma associated with eye rubbing may be the etiologic 19 concordant pairs have been reported since the advent of corneal
link between conical cornea and associated systemic and ocular dis- topography.46–49
eases. Itching, ocular irritation, and eye rubbing are common features McMahon et al.50 described two pairs of discordant monozygotic
of vernal keratoconjunctivitis and atopic disease. Vigorous eye rubbing twins, in which one of each pair had keratoconus and the other had
has frequently been observed in patients with Down syndrome and normal corneal topography in both eyes. It was suggested that an envi-
may explain the high incidence of associated corneal hydrops. Finally, ronmental trigger might be necessary in addition to a genetic predis-
eye rubbing is commonly seen in poorly sighted patients with Leber position or that genetic differences between the individuals may exist,
congenital amaurosis and retinopathy of prematurity, both of which even in monozygotic twins. A “two-hit” hypothesis, that is, genetic pre-
are associated with keratoconus. Bawazeer et al.35 found that while disposition plus environmental insult, such as eye rubbing, is a leading
atopy, eye rubbing, and family history of keratoconus were all associ- theory on the development of keratoconus.34
ated with the development of keratoconus, only eye rubbing reached The frequency of inheritance has been estimated to be 6%.51 Cor-
statistical significance on multivariate analysis. neal topography has been used to examine family members of kera-
Contact lens wear is another form of corneal microtrauma that toconus patients.52–54 Corneal contour abnormalities were uncovered
is associated with keratoconus. Retrospective studies have found a in some clinically unaffected relatives. Whether these patients would
history of contact lens wear before the diagnosis of keratoconus in progress to clinically significant disease is unknown. This evidence has
17.5%36–26.5%37 of cases. A retrospective review37 identified a sub- supported a pattern of autosomal dominant inheritance with incom-
group of keratoconus patients who were not thought to have had the plete penetrance. The information gathered using corneal contour
condition before beginning contact lens wear. These long-term contact imaging may help create more accurate pedigrees in families with ker-
lens wearers were older and tended to have central cones and flatter atoconus, which could be used in future genetic study.
corneal curvature than keratoconus patients with no history of contact Molecular genetic techniques are being used to study candidate
lens wear before diagnosis. genes for proteins that may be involved in the development of kera-
toconus, for example, genetic changes in the collagen pathway, the
Biochemistry interleukin-1 system, proteases, and protease inhibitors.54–56 Linkage
Biochemistry has provided an important line of research into the eti- analysis has been utilized to map susceptible genetic loci, and many
ology of keratoconus. Since much of the work has been done on host distinct genomic loci have been mapped to the disease, indicating a
corneas following PKP, it is important to keep in mind that the results high degree of genetic heterogeneity. Most of these loci were isolated in
of many of these studies relate more to advanced keratoconus. large keratoconus pedigrees. Despite efforts to screen numerous can-
The total amount of protein is decreased in keratoconus.38 Theoret- didate genes within these loci, identification of causative genes (and
ically, an upregulation of degradative enzymes and the downregulation mutations) remains a challenge.
of proteinase inhibitors could result in a degradation of the extracellu- Patients commonly ask if keratoconus is inherited and if their chil-
lar matrix of the stroma. The level of degradative lysosomal enzymes, dren will develop the disorder. Review articles regarding the genetics of
such as acid esterase and acid phosphatase, cathepsins B and G, and keratoconus focus on the genetic risk factors and possible genetic links
some matrix metalloproteinases, has been shown to be elevated in ker- to comorbidities.12,57 Using clinical evaluation and three keratographic
atoconus corneas.39,40 These findings are predominately present in the indices, Wang et al.58 found the keratoconus prevalence of first-degree
corneal epithelium. relatives to be 3.34%, which is up to 68 times that found in the general
If an enzymatic imbalance within the epithelium alone caused ker- population. It seems reasonable to tell parents that the chance that a
atoconus, one might expect a significant recurrence rate following a first-degree relative would be found to have symptoms of the disease,
corneal graft after replacement with host epithelium. In fact, the recur- while significantly greater than the general population, is still less than
rence rate following PKP is low. One must assume that the pathogen- 1 in 20. Future studies based on anterior segment optical coherence
esis of keratoconus is more complex than the preceding theory would tomography (AS-OCT)59 or Scheimpflug tomography60 rather than
suggest. Placido-based systems may result in a higher incidence of subclinical
Keratocytes from keratoconus corneas have been found to have keratoconus.
four times the interleukin-1 binding sites, compared to nonkerato- The phenotypic appearance commonly recognized as keratoconus
conus corneas.41,42 This may result in an increased sensitivity to the may occur in patients having multiple genotypes. Keratoconus study
effects of interleukin-1, which has been shown to induce apoptosis of populations that have associated ocular or systemic diseases in com-
stromal keratocytes in vitro. Apoptosis has been found in the stroma mon or contour characteristics in common may be more likely to share
of keratoconus corneas, but not in normal controls.43 Wilson et al.44 a common genotype. Identifying such specific study groups is essential
postulated that the corneal epithelium might release interleukin-1 in in the genetic study of keratoconus.12,57
response to microtrauma occurring after eye rubbing or contact lens
wear. This in turn could trigger apoptosis of stromal keratocytes in ker- Pathology
atoconus patients with heightened sensitivity to interleukin-1. Every layer and tissue of the cornea can potentially be involved in the
pathologic process of keratoconus. Central epithelial thinning has been
Heredity found with variable frequency.61 In contrast, thickening of the epithe-
The most compelling evidence for a genetic origin in some forms of lium has been demonstrated on clinical imaging with AS-OCT.62 Spec-
keratoconus is the degree of concordance between monozygotic twins. ular microscopy of the corneal epithelium has revealed enlargement of
There are reports of at least 18 sets of monozygotic twins45 that identify the superficial cells and prominence of elongated cells, specifically over
one or both siblings in the pair with evidence of keratoconus. Seven the apex of the cone. These findings were not seen in long-term hard
of the 18 pairs evaluated without corneal topography were concordant contact lens wearers.63 TUNEL-positive epithelial cells were detected
for keratoconus. Edwards et al.45 correctly point out that the evidence in deeper epithelium, signifying apoptosis and cell death in an atopic
of discordance cannot be considered conclusive in the absence of animal model, with findings consistent with keratoconus.64 Early
CHAPTER 73 Noninflammatory Ectatic Disorders 753
1 1
Fig. 73.3 Breaks in the Bowman layer fill in with collagenous scar tis-
sue (1) (hematoxylin and eosin stain, ×400). This process results in the
reticular, subepithelial, and anterior stromal scars typical of keratoconus.
It has been suggested that collagen lamellae are released from their
interlamellar attachments or from their attachments to BL and become
free to slide. This results in thinning without collagenolysis.71 The
interlamellar strength profile in the normal cornea has been found to
$
be significantly weaker inferiorly and centrally.72 Significant alteration
of the normal orthogonal arrangement of the collagen fibrils found
in keratoconus may be related to this biomechanical instability of the
stromal tissue.73 The most common location for the apex of the cone,
in the central or inferior cornea, may be related to this inherent corneal
weakness. This may also explain the association of eye rubbing with
keratoconus.74
% Endothelial cell pleomorphism and polymegethism occur in ker-
atoconus, but may simply be related to long-term contact lens wear
Fig. 73.2 The Fleischer ring in keratoconus. (A) The Fleischer ring (1) rather than keratoconus.75 Patterns of endothelial damage vary from
is a landmark indicating the location of the base of the cone; (2) pupil isolated cell membranolysis to denudement of the Descemet mem-
margin. (B) The ring results from hemosiderin pigment deposited in the brane. More damage occurs at the base of the cone than at the apex and
basal epithelium (Prussian blue stain, ×200).
correlates with the severity and duration of the disease.76
Fig. 73.4 Angulation of the lower lid in downgaze known as Munson Fig. 73.5 A hallmark of keratoconus is corneal thinning, which occurs
sign, which is a nonspecific sign of advanced keratoconus. at the cone apex, the point of maximal protrusion. Scarring may induce
flattening at the apex of the cone. Corneal flattening is commonly seen
can occur.78–80 Anterior surface power maps demonstrate that inferior superior to the cone.
steepening in keratoconus is associated with superior flattening.81
Corneal thinning is observed at the apex of the protrusion
(Fig. 73.5). Two types of cones have been described.68 The round
or nipple-shaped cone is smaller in diameter, while the larger oval
or sagging cone may extend to the limbus and is more likely to be
associated with contact lens fitting problems.
Keratoconus is in the differential diagnosis of prominent corneal
nerves and when observed it is usually mild and localized.82 Vogt striae
(Fig. 73.6) occur in the posterior stroma just anterior to Descemet
membrane. When the intraocular pressure is transiently raised, by
applying external pressure to the globe, the striae disappear. These fine
parallel posterior striae should be distinguished from the superficial
reticular scars seen at the cone apex, which result from ruptures in BL.
Subtle superficial anterior clear spaces have been identified at the slit
lamp in 38% of 69 consecutive keratoconus cases.67
The CLEK study has found that corneal scarring in keratoconus
is associated with reduced high- and low-contrast visual acuity and
increased symptoms of glare.11 Factors predictive of corneal scarring
include corneal power greater than 52 diopters (D), contact lens wear,
corneal staining, and age less than 20 years.83 Scarring was more than
three times as likely to be found in association with a flat-fitting contact
lens.84 Contact lenses that reduce apical touch may reduce the inci-
dence of corneal scarring. However, patients with steeper corneas are
more likely to scar even without contact lens wear.83
In more advanced cases, deeper opacities can be seen at the apex of
the cone, resulting from ruptures in the Descemet membrane. Acute
keratoconus or corneal hydrops results from stromal imbibition of Fig. 73.6 Vogt striae are fine posterior stromal folds often noted ante-
aqueous through these ruptures (Fig. 73.7A and B). If untreated, the rior to Descemet membrane at the apex of the cone. They tend to dis-
edema may persist for weeks or months, usually diminishing gradually. appear when external pressure is applied to the eye.
Eventually, it is replaced by scar tissue, which in some cases may result
in flattening of the conical contour. blue illumination in the widest possible slit beam can be used in early
Corneal pseudocysts or intrastromal clefts (Fig. 73.7C) have been cases to enhance the visibility of a subtle iron ring.
described in association with hydrops in keratoconus.85,86 Single or The manual keratometer is a helpful tool for measuring anterior
multiple clefts can occur, and bilateral involvement is possible. Clefts corneal curvature. Inability to superimpose the central keratometric
usually close within 6 months, but stromal neovascularization is com- rings suggests irregular corneal astigmatism, a sign of keratoconus.
mon and can affect future graft survival. The presence of large intra- There is no keratometric value beyond which the diagnosis of kerato-
stromal clefts may explain how corneal perforation can occur after conus is definite. There are patients with steep corneas and high astig-
minor trauma in cases of keratoconus with hydrops. matic errors who do not have keratoconus and, conversely, patients
The Fleischer ring (see Fig. 73.2A), a partial or complete annular with keratoconus who have normal or relatively flat central corneal
line, is commonly seen at the base of the corneal protrusion. When contour. Inferior corneal steepening is also an early sign of keratoco-
identified, it provides a landmark for the peripheral edge of the cone. nus. By performing central keratometry, followed by keratometry with
As the ectasia progresses, the ring tends to become more densely pig- the patient in upward gaze, steepening in the inferior cornea can be
mented and narrower, and it may completely encircle the cone. Cobalt identified and documented.
CHAPTER 73 Noninflammatory Ectatic Disorders 755
Corneal Power
Rabinowitz has suggested four quantitative Placido-based indices as an
aid for screening patients for keratoconus.97 These indices include cen-
tral corneal power value greater than 47.2 D, inferior/superior diop-
tric asymmetry (I-S value) greater than 1.2, Sim-K astigmatism greater
than 1.5 D, and skewed radial axes (SRAX) greater than 21 degrees.
These indices were used to distinguish keratoconus from normal cor-
neas and were most effective when corneal astigmatism was greater
than 1.5 D. Evolution in keratoconus detection has resulted in contin-
ued refinement of the neural network approach by Smolek and Klyce98
and the KISA% index described by Rabinowitz and Rasheed.99 Both
systems purport an ability to detect keratoconus suspects and grade the
severity of keratoconus.
& One should be mindful that inferior steepening on a power map
can result from poor patient fixation,100 misalignment of the video-
Fig. 73.7 Corneal hydrops in keratoconus. (A) Ruptures in the Descemet keratograph,101,102 dry spots on the cornea, inferior eyeball compres-
membrane permit the stromal imbibition of aqueous and result in the sion,15 and contact lens–related corneal warping.103 Suspicion should
marked corneal edema seen in this slit lamp photograph. Keratoplasty is be raised if the map is grossly inconsistent with other aspects of the
usually necessary if edema persists beyond 3 months or if scarring is exten-
imaging analysis.
sive or is in the central cornea. (B) Anterior segment optical coherent tomog-
raphy shows a Descemet membrane detachment associated with corneal
hydrops. (Courtesy Asim Farooq, MD.) (C) Intrastromal fluid-filled clefts can
sometimes occur, as seen in this slit view. Clefts can be single or multiple
and usually close, but may be associated with increased neovascularization.
756 PART VII Diseases of the Cornea
Fig. 73.8 Corneal topography and tomography are useful in detecting keratoconus at various stages of progression. Representative stages of
disease are demonstrated. (A) Subclinical keratoconus. Orbscan II (Bausch & Lomb) anterior elevation map (upper left) shows an eccentric area of
elevation, posterior float (upper right) shows prominent elevation coincident with the anterior elevation, power map (lower left) shows asymmetric
dumbbell with mild skewing of radial axes and superior flattening, pachymetry map (lower right) shows point of maximal thinning eccentric and coin-
cident with elevation on anterior and posterior float maps. Even the thinnest part of this cornea (518 μm) is within the range of normal. (B) Moderately
advanced keratoconus. Pentacam (OCULUS, Wetzlar, Germany) power map, upper left, shows moderate inferior steepening, superior flattening,
and corneal astigmatism measuring 8.1 D and steepest power, Kmax, 62.7 D; prominent islands of elevation are noted anteriorly, upper right, and
posteriorly, lower right; eccentric and abnormal corneal thinning is noted in the pachymetry map, lower left, with the thinnest cornea measuring 368
microns. Maximum thinning, protrusion, and steepening are coincident in this cornea.
CHAPTER 73 Noninflammatory Ectatic Disorders 757
Corneal Elevation and Thickness keratoconus patient in this way over time and detecting progression
The scanning-slit topography device (Orbscan II, Bausch & Lomb) earlier may help preserve vision by permitting intervention at an earlier
provides a power map, a pachymetry map, and maps based on eleva- stage.
tion relative to a best-fit sphere. These consist of an anterior elevation
map (anterior float) and a mathematically derived posterior elevation Biomechanical Measurement
map (posterior float) (see Fig. 73.8A). The elevation difference front to The Ocular Response Analyzer (Reichert Technologies, Buffalo, NY)
back should not exceed 40 μm if laser in situ keratomileusis (LASIK) is is capable of directly measuring biomechanical properties of the cor-
being considered. Values greater than 50 μm are suggestive of kerato- nea in response to an air puff. Both corneal hysteresis, which indicates
conus. The posterior float is the least reliable of the four maps.104 The the viscoelasticity of the cornea, and the cornea resistance factor are
pachymetry map gives a relative overview of corneal thickness, but the depressed in patients with corneal ectasia. These indicators can be
values should not be considered equivalent to pachymetric readings used in addition to corneal tomography to evaluate patients at risk for
measured by ultrasound or Scheimpflug photography. corneal ectasia. The Corvis ST (Oculus Optikgeräte GmbH, Wetzlar,
Scheimpflug-based tomography is a more accurate means of mea- Germany), not currently available in the United States, employs a non-
suring corneal elevation and thickness (see Fig. 73.8B). A virgin cornea contact tonometer to monitor the response of the cornea to an air pres-
with an isolated island of anterior elevation measured with the Pen- sure pulse captured with ultra-high speed Scheimpflug photography.109
tacam, which exceeds the best-fit sphere by more than 11 μm, and/or The Corvis Biomechanical Index (CBI) based on corneal thickness
posterior elevation greater than 20 μm is suspicious for an ectatic cor- profile and deformation parameters was shown to be highly sensitive
neal contour. Posterior elevation may be the first indication of ectatic and specific in separating healthy from keratoconic eyes.110
disease. The Pentacam software can enhance the detection of early ker-
atoconus by analyzing elevation data, excluding the area around the Treatment
thinnest part of the cornea from best-fit sphere calculations, increas- The management of keratoconus is focused on two important goals:
ing the sensitivity of detection of islands of elevation (Fig. 73.9A). In arresting progression and providing visual rehabilitation. Patients with
addition, the change in corneal thickness starting from the thinnest keratoconus should be reminded to avoid eye rubbing and any asso-
position on the cornea and moving outward toward the periphery can ciated atopic disease should be optimally managed. Patients can often
be used to determine the rate of thickness change in comparison to tolerate higher degrees of astigmatism and anisometropia than normal
normative data (see Fig. 73.9B). The Scheimpflug-based Keratoco- patients; however, when glasses fail to provide adequate visual function,
nus Assistant (KA), a program developed for automatic detection of contact lens fitting is indicated. Surgery is considered when patients
keratoconus by using 25 Pentacam-derived parameters, was recently cannot tolerate or are not fully satisfied with nonsurgical treatments.
validated with an accuracy of 98.9% and sensitivity of 99.1% in differ- CXL, recently approved in the United States, has the potential to arrest
entiating keratoconus eyes from normal eyes.105 progression of keratoconus, particularly in mild to moderate disease.
AS-OCT was first applied by Li et al.106 to obtain precise pachymet-
ric maps in keratoconus (Fig. 73.10A and B). The authors established Contact Lens
five OCT parameters felt to be consistent with keratoconus. Kanel- Contact lens wear improves visual function by creating a new anterior
lopoulos et al.62 found using AS-OCT that there is increased overall refractive surface (Fig. 73.11). Contact lenses do not prevent progres-
thickness and increased variation. It is possible that this increased sion of corneal ectasia. While they appear to be associated with the
epithelial thickness may compensate for underlying irregular stromal development of keratoconus in some cases, this important mode of
distribution, thus masking early stage keratoconus on other imaging therapy should not be withheld for fear of causing progressive disease.
devices. Li et al. reports that pattern analysis of the corneal and epi- Contact lens fitting must be tailored to the individual’s visual needs
thelial thickness maps derived by Fourier-domain OCT could detect and comfort tolerance. Given ample time and motivation, fitting exper-
early keratoconus.59 In a study comparing asymmetric keratoconus tise, and access to all available contact lens modalities, many keratoconus
(AKC) from a normal control population, Hwang et al.107 found that patients can achieve good visual function with a stable, well-tolerated lens.
combining anterior curvature and asymmetry indices from Scheimp- Soft contact lenses may be effective for patients with mild disease.
flug photography with regional total thickness and epithelial thickness As the ectasia progresses, various gas-permeable hard lens options and
variability metrics from spectral domain OCT effectively distinguished specialty lenses are available. Relatively flat-fitting, rigid gas-permeable
the 2 populations. This highlights the improved detection of kerato- (RGP) hard contact lenses with light apical corneal touch, the so-called
conus obtained by combining data derived from various imaging three-point touch technique, remains the mainstay of contact lens treat-
technologies. ment for keratoconus.111,112 Apical touch has been associated apical
An important consensus of the Delphi panel on keratoconus and scarring.83 An apical clearance fitting technique is also commonly used.
ectatic disease4 concluded there was no appropriate classification sys- Other options include soft toric lenses, standard bicurved hard lenses,
tem for keratoconus and no effective way to assess progression. Histor- custom back-toric lenses, scleral lenses, and mini-scleral lenses.113
ical classification systems such as the Amsler-Krumeich system or the Hybrid lenses,114 such as the SoftPerm lens (CIBA Vision Corp., Duluth,
CLEK11 system do not consider diagnostic information provided by GA, USA) and SynergEyes KC lens (SynergEyes, Inc., Carlsbad, CA,
current technology. Classification of keratoconus is important not only USA), and piggyback systems may be more comfortable for patients
to characterize the current status, but also to track progression. The who cannot tolerate an RGP alone.
ABCD keratoconus grading system108 (Table 73.3) relies on corneal The Rose K system (Menicon America, Inc., Waltham, MA, USA) is
tomography. It is based on an evaluation of a 3 mm area around the site an additional option for keratoconus patients unable to wear conven-
of thinnest pachymetry, specifically anterior radius of curvature (A), tional RGP lenses.115 The trial set contains lenses with posterior curves
posterior radius of curvature (B), thinnest pachymetry reading (C), that more closely fit the abnormal conical contour.
and distance visual acuity (D) to stage the disease. The cornea is staged Scleral and mini-scleral lenses have become increasingly popular in
grade 0 to grade IV. It can also be used to identify progression over time the management of corneal ectasia. These lenses rest on sclera but do
within the various parameters. Progression is defined as a worsening of not touch cornea or limbus, providing a tear fluid reservoir, correct-
1 parameter to a 95% CI or 2 parameters to an 80% CI. Tracking the ing astigmatism, and improving comfort and stability.116 Mini-scleral
758 PART VII Diseases of the Cornea
%
Fig. 73.10 Anterior segment optical coherent tomography (OCT) can
be used to generate cross-sectional images of the cornea. These can
be used to create anterior and posterior corneal power, elevation, and
pachymetry maps. The image above (A) based on spectral domain OCT
technology demonstrates apical thinning as well as anterior stromal scar-
ring near the apex of the cone. Below (B) is the associated pachymetric
map. (Optovue, Freemont, CA.) (Courtesy Robert Weisenthal, MD.)
%
sites around the country and can improve visual function with a com-
Fig. 73.9 Accurate measurements of elevation and pachymetry using fortable and stable-fitting lens.118,119 This system has the advantage of
Scheimpflug technology can be used for enhanced keratoconus detec- eliminating apical touch.
tion. (A) The Pentacam (OCULUS) subtracts an area encompassing the One form of contact lens intolerance may result from epithelial
thinnest part of the cornea from the calculation of the best-fit sphere breakdown overlying a subepithelial fibrotic scar occurring at the apex
anteriorly and posteriorly (middle right and left), which highlights an of the cone. Using a self-retaining wire speculum and topical anesthe-
island of elevation (middle right) and generates a difference map (lower sia, this fibrotic nodule is easily debrided at the slit lamp. After the cor-
right and left). (B) Accurate measurements of corneal thickness using
nea has healed, the patient may resume contact lens wear, obviating the
Scheimpflug technology and the Pentacam software produce analyses
of thickness progression from thinnest part of the cornea to the periph-
need for more invasive surgery. Phototherapeutic keratectomy (PTK)
ery. Patient curves that extend below the normative curves are sugges- has also been used in this setting.120 While it may be helpful in some
tive of ectatic disease. The indices below indicate significant deviation cases, PTK may cause keratolysis,121 increased scarring, and ectasia,
from the mean of each parameter consistent with corneal ectasia. thereby hastening the need for PKP.
lenses (15.0–18.0 mm) such as MSD (Blanchard Contact Lens, Inc., Intrastromal Ring Segments
Manchester, NH, USA) and Maxim (Acculens, Denver, CO, USA) Contact lens-intolerant keratoconus patients without central scarring,
have scleral bearing and minimal corneal clearance. Full scleral lenses who have mild or moderate disease, may be candidates for intrastromal
(18.1–24.0 mm) such as Jupiter (Medlens Innovations, Front Royal, VA ring segment insertion (Fig. 73.12A). The ideal candidates also have low
or Essilor Contact Lens, Inc., Dallas, TX, USA) and Tru-Scleral lens spherical equivalents and average keratometry readings of less than 53
(Tru-Form Optics, Bedford, TX, USA) have scleral bearing and max- D. The procedure improves visual acuity by flattening the central cor-
imum corneal clearance.117 They are advantageous for patients with nea, reducing astigmatism, and centering the cone.122–125 The goal of the
more irregular corneas and delay the need for keratoplasty in eyes with procedure is to improve contact lens fit and comfort. It may also improve
advanced keratoconus. best spectacle-corrected visual acuity (BSCVA). It is important to set
PROSE treatment, which utilizes a custom lathed scleral lens devel- proper patient expectations prior to surgery and inform the patient that
oped by the Boston Foundation for Sight, is now available at multiple glasses and/or contact lenses will still be needed after surgery.
CHAPTER 73 Noninflammatory Ectatic Disorders 759
Fig. 73.11 The effect of hard contact lens wear on the anterior refractive surface in a case of advanced kera-
toconus. (1) Without the contact lens a scarred, markedly flat cone apex is seen. (2) This correlates with the
variably spaced rings in this irregular keratograph. (3) With a hard contact lens on the same cornea the power
map has an appearance approaching normal. (4) This is verified in the keratograph on the lower left in which
the edge of the contact lens can be seen.
To achieve the desired effect, the ring segments must be inserted at The procedure in its classic form, the Dresden protocol, begins with
approximately two-thirds depth; therefore the cornea should be at least the removal of the central epithelium to enhance stromal saturation
450 μm thick (see Fig. 73.12B). Ring segments are available in various with the topically applied riboflavin (vitamin B2). The cornea is then
thicknesses, and enhanced effect is generally achieved with the thicker irradiated with ultraviolet A (UVA) light at 370 nm for 30 minutes (Fig.
segments. Stromal channels of the appropriate width and depth can be 73.13A). The irradiation of the riboflavin results in chemical reactions
prepared with a specially designed keratome or femtosecond laser.126 that create covalent bonds, which bridge amino groups of the stromal
While wide channels make insertion easy, the desired effect can only be collagen fibrils.130
obtained with a snug fit. Colin and Malet124 reported that contact lens The principal effects of crosslinking are localized to the anterior
wear was restored in over 80% of cases. 300 μm of the stroma.131 The biomechanical effect in human corneas
While the ring segments are removable, the procedure should not be is a 328.9% increase in corneal rigidity.132 Increased resistance to enzy-
considered completely reversible. The ring segments do not prevent pro- matic degradation shown in porcine eyes following crosslinking may
gression of the underlying disease. If keratoplasty later becomes necessary, also contribute to biomechanical stability.133
the surgery should occur at least 1 month following ring segment removal. The improvement in visual acuity after CXL is the result of
decreasing both corneal curvature and astigmatism. Raiskup-Wolf
Corneal Crosslinking et al. reported a 2.68 D reduction in corneal power at 1 year postop-
CXL may slow or halt the progression of keratoconus by using a eratively.127 Three years after the treatment, the BCVA improved one
photo-oxidative treatment to increase the rigidity of the corneal line in 58% of 33 eyes and remained stable in 29% of eyes (P < .01).
stroma.127–129 While widely used outside the United States for many The astigmatism had diminished by a mean of 1.45 D in 54% of eyes.
years, CXL has more recently become FDA approved for use in the The induced topographic changes have the potential to improve con-
United States. tact lens fit. CXL appears to be most beneficial for patients with mild
760 PART VII Diseases of the Cornea
Keratoplasty
When a stable, comfortable contact lens fit cannot be obtained or fails
to provide adequate vision or when significant corneal scarring is pres-
ent, the cornea is very thin (<200), or when corneal hydrops fails to
resolve, a more invasive surgery such as keratoplasty is recommended.
The type of keratoplasty depends on the individual patient’s needs and
the surgeon’s preference. While PKP has traditionally been the surgery
of choice, lamellar surgery has definite advantages for patients with
mild to moderate disease. Recurrent keratoconus in the donor follow-
ing cornea transplant has been reported;145,146 however, recurrent ker-
atoconus is far more likely to be related to incomplete excision of the
cone. The iron ring, found at the base of the cone, should be used as a
reference when planning graft size.
Post-keratoplasty myopia can be reduced by using the same-sized
donor and host corneal buttons.147–150 Some have even suggested
% undersizing the donor to further flatten the postoperative corneal con-
tour.151 In order to prevent postoperative hyperopia, same-size donor
Fig. 73.12 Intracorneal ring segments. (A) Diffuse illumination reveals
and host corneal buttons should be avoided when the anterior lens-
two ring segments in a keratoconus cornea. (B) Slit view demonstrates
the appropriate depth for ring segment placement.
to-retina length is less than 20.19 mm, the mean length for normal
emmetropic individuals.152
DALK is an alternative to PKP. It is not recommended, however,
progressive keratoconus. It is less effective in patients with advanced in cases of deep stromal scarring or after corneal hydrops. Since
keratoconus. CXL has been shown to halt progression of ectasia fol- the host endothelium is preserved, the risk of endothelial rejection
lowing LASIK and PRK, but the effect is less pronounced than in is eliminated. Stromal rejection is still possible and occasionally
keratoconus.134 problematic. The risk of endophthalmitis is theoretically less in this
CXL poses a risk of dose-dependent keratocyte apoptosis affecting largely extraocular procedure. In the event of trauma, intact host
the anterior 300 μm of the cornea (see Fig. 73.13B). UVA irradiance Descemet membrane occurring after DALK affords greater wound
CHAPTER 73 Noninflammatory Ectatic Disorders 761
A B
Fig. 73.13 (A) Cornea crosslinking treatment on a patient using riboflavin/ultraviolet A (UVA). Appearance of
the red cross-hairs ensures that the UVA source is a proper distance from the cornea. A 9 mm epithelial defect
has been created and the stroma saturated with topical riboflavin according to the Dresden protocol. The
stroma must be at least 400 μm to control the risk of endothelial cytotoxicity. (B) Light microscopy 24 hours
after crosslinking in human cornea showing depletion of keratocytes down to 250 μm. Note the absence of
inflammatory cells in the treated anterior cornea due to apoptosis. (Hematoxylin and eosin stain, magnifica-
tion ×200.) (Image courtesy of Gregor Wollensak, MD and Eberhard Spoerl, PhD.)
stability than occurs following PKP. High postoperative astigmatism Bowman Layer Transplantation
can still occur after DALK, just as in full-thickness surgery. Visual BL transplantation is a novel surgical technique introduced by Dijk
outcomes are comparable to PKP153,154 provided the residual stro- et al.159 The goal of BL transplantation is to implant donor BL to the host
mal bed thickness is minimized. Late reduction of endothelial cell mid-stroma through a scleral tunnel. Twenty-two eyes of 19 patients
density postoperatively is less than PKP.155 DALK is technically followed for 3 years demonstrated improvement in BCVA, reduction of
more challenging and time-consuming, which may explain its lim- mean keratometry by approximately 8 D, and a 28 μm increase in cor-
ited popularity. There are various DALK techniques such as the big neal thickness. Advantages are preservation of the host endothelium,
bubble technique,156 manual layer-by-layer pre-Descemetic DALK reduction in graft rejection, and reduction in steroid use.160
(pdDALK), pdDALK with viscodissection, pdDALK with the light
reflex guided Melles technique,157 and femtosecond laser-assisted Post-Keratorefractive Surgery Corneal Ectasia
dissection. Post-keratorefractive ectasia resembles keratoconus, with the typical
The treatment of keratoconus is rarely an emergency. The exception clinical and tomographic findings of progressive thinning and pro-
is corneal hydrops, resulting from a rupture in the Descemet mem- trusion and resultant loss of visual function. Ectasia can present years
brane (see Fig. 73.7B). The break in the Descemet membrane can be after laser refractive surgery and can occur in some patients even in the
identified using AS-OCT or ultrasound biomicroscopy (UBM). A dra- absence of any apparent risk factors.161,162
matic reduction in vision occurs due to marked stromal edema. This An understanding of cornea stromal ultrastructure and biome-
may be accompanied by redness, discomfort, and photophobia. Proper chanics can help explain how ectasia can develop in some cases.
management includes patching or bandage contact lens, topical cyclo- Dawson et al.163 have shown that the anterior and peripheral stroma
plegia, hypertonic sodium chloride ointment and/or drops, and reas- are more rigid and have greater cohesive tensile strength than the
surance. Topical steroids are rarely needed. posterior two-thirds of the stroma. They concluded that this is per-
Intracameral air has been used in the management of corneal haps related to observed differences in the direction of collagen fibrils
hydrops. The air acts as a mechanical barrier, reducing aqueous flow between the anterior and posterior stroma and/or the degree of col-
into the stroma through the rupture. Because the air is absorbed over lagen lamellar interweaving in BL. Stromal ablation into the poste-
a few days, the longer lasting intracameral gasses sulfur hexafluoride rior stroma could potentially create a postsurgical cornea with less
(SF6) and perfluoropropane (C3F8), in isoexpansile concentrations, are rigidity and cohesive tensile strength. This situation would arise if the
advantageous. C3F8 in 14% concentration may persist in the anterior degree of myopia is high, the cornea is thin, or the flap is uninten-
chamber up to 6 weeks. A concentration of 20% SF6 gas is nontoxic tionally thick.
to the endothelium and can last up to 2 weeks. The pupil should be Patients with an abortive form of ectasia, the so-called forme fruste
dilated and laser peripheral iridotomy should be considered to prevent disease, might remain in the subclinical state if left untouched. A
pupillary block. Panda et al. reported the safety and efficacy of SF6 in young patient may develop manifest disease in the absence of surgery
expediting resolution of corneal edema.158 Hydrops that does not clear if followed over time. Brenner et al.164 found preoperative forme fruste
by 3–4 months is best treated by PKP. keratoconus in 58 of 77 patients with post–LASIK ectasia. In another
762 PART VII Diseases of the Cornea
%
$
Fig. 73.14 Pellucid marginal degeneration appearance. (A) The profile of a cornea with pellucid marginal
degeneration shows protrusion and sagging of the inferior cornea. (B) This slit lamp photograph demonstrates
corneal protrusion superior to the point of maximal thinning.
study165 forme fruste disease was a risk factor in 21.4% of postoperative is usually found 1–2 mm central to the inferior limbus. Atypical
ectasia patients. It is imperative to successfully identify these patients cases of PMD with thinning extending beyond the inferior 4 o’clock
and counsel them against LASIK surgery. hour occur,167 as do cases in which the thinning is confined to a
With the advent of newer technologies, for example, Scheimpflug superior location.168,169 At least 6 cases of unilateral PMD have been
photography and AS-OCT, more accurate elevation maps have become reported.170
useful tools for detecting subclinical disease (see Fig. 73.9A). Isolated In contrast to keratoconus, maximal corneal protrusion typi-
islands of elevation, significant differences in thickness between the two cally occurs just superior to, rather than within, the area of thinning
eyes, or areas of eccentric thinning are all helpful indicators. The rate (Fig. 73.14). The result is a corneal contour reminiscent of a “beer
of corneal thickening moving from the thinnest point to the periphery belly.” The protruding cornea is of normal thickness. The abnormal
can also be suggestive of ectasia (see Fig. 73.9B). Proper preoperative corneal contour induces a shift in the axis of astigmatism from against-
evaluation requires the refractive surgeon to use multiple maps and the-rule, superiorly, to with-the-rule, near the point of maximal pro-
analyses before concluding that the risk of ectasia following keratore- trusion. PMD and keratoconus can occur in the same eye.171 The two
fractive surgery is minimal. diseases can also be seen in the same family.29
Randleman et al.166 studied patients with post-LASIK ectasia and Patients with this condition usually present for treatment between
identified five main risk factors for this complication. These included the second and fifth decades of life complaining of blurred vision due
young age at the time of surgery, abnormal preoperative topography, to irregular astigmatism. There is no racial or gender predisposition.
reduced residual stromal bed thickness, decreased preoperative cornea Maguire et al.172 have described the corneal contour in PMD
thickness, and high myopia. These variables were incorporated into a using power maps. The typical crab-claw (Fig. 73.15) illustrates the
scoring algorithm to quantitatively assess the risk of ectasia. Binder and shift in astigmatism from the superior to the inferior cornea. The
Trattler conducted a large retrospective review to evaluate Randleman’s crab-claw appearance on a power map can also occur in patients with
ectasia risk scores. They found that in patients with normal preopera- inferior keratoconus and tomography is helpful to differentiate the
tive topographies, the scoring system may not predict an increased risk two conditions.
of postoperative LASIK ectasia.162 Tatar et al.165 found deep ablation Patients with PMD are poor candidates for refractive surgery
(>75 µ) to be the most significant risk factor, but 21.4% (9/42) had no because of the risk of progressive ectasia. Review of corneal topogra-
preoperative ectasia risk factor. phy as well as tomography can help identify the patient with contour
abnormalities even when the best corrected acuity is 20/20.
The corneas in PMD are generally clear and avascular. The typical
PELLUCID MARGINAL DEGENERATION findings of keratoconus, protrusion within the area of corneal thin-
PMD is a bilateral, peripheral corneal ectatic disorder characterized ning, striae, and iron ring, are not seen in PMD. Stromal scars have
by a band of thinning 1–2 mm in width, typically in the inferior cor- been described at the level of the Descemet membrane extending into
nea, extending from the 4 to 8 o’clock position. The area of thinning the mid-stroma, located at the superior aspect of the thinned area.
CHAPTER 73 Noninflammatory Ectatic Disorders 763
Fig. 73.15 Pellucid marginal degeneration—or is it? The power map upper left shows the classic crab-claw
configuration often seen in pellucid marginal degeneration; however, the pachymetry map, lower left, fails to
show a band of thinning inferior to the protrusion noted on the elevation maps, upper right and lower right.
This is actually an inferior cone and illustrates the need to look beyond Placido-based topography to make the
correct diagnosis.
While the cornea can become quite thin, rupture rarely occurs.173,174 not been well studied in this setting. Alternative surgical procedures
Hydrops can occur, resulting in edema, scarring, and vascularization include crescentic lamellar keratoplasty182 and crescentic wedge exci-
of the inferior cornea. sion.183 Long-term astigmatism drift may be a problem following
Spectacles usually fail to adequately correct the high irregular resection procedures.
astigmatism associated with PMD. Large-diameter, RGP contact
lenses can be tried. However, a stable long-term fit can be difficult
to achieve. The hybrid lenses and scleral lenses have been used suc-
KERATOGLOBUS
cessfully in PMD.175 These patients are also candidates for PROSE Keratoglobus is a bilateral ectatic disorder that is usually nonprogres-
treatment.118 sive or minimally progressive. The typical globular protrusion of the
A surgical approach may be required for visual rehabilitation. cornea results from generalized thinning, most marked in the periph-
Large-diameter or eccentric PKP is usually required to encompass the ery (Fig. 73.16). Associated scleral thinning has also been described.184
area of peripheral thinning. Placing the graft wound in proximity to the While minimal corneal scarring may be seen, an iron ring is not
limbal vasculature increases the risk of endothelial rejection. Success observed. The cornea is of normal or slightly increased diameter.
with large-diameter PKP in the absence of corneal neovascularization Acute hydrops occurs less frequently than in keratoconus;185 however,
has been reported.176 Varley et al.177 reported a rejection rate of 64%, the opposite is true about corneal perforation and rupture. Corneal
but none of the 12 large, eccentric grafts failed because of rejection over rupture can occur after minimal trauma.
a mean follow-up period of 3 years. The corneal topography and tomography in patients with kerato-
Newer surgical techniques are being used in the treatment of globus have not been well described. The central and paracentral eleva-
PMD.178,179 DALK has the advantage of eliminating the risk of endo- tion and steepening with generalized thinning one might expect to see
thelial rejection completely; stromal rejection is still problematic, is demonstrated in Fig. 73.17. Keratoglobus can occur in the fellow eye
however. CXL180 and ring segments181 have been described but have of a patient with PMD.
764 PART VII Diseases of the Cornea
1 POSTERIOR KERATOCONUS
In posterior keratoconus, thinning results from an increase in the cur-
vature of the posterior cornea. Corneal involvement can be diffuse
or localized. In keratoconus posticus generalis, the entire posterior
corneal surface has an increased curvature and the cornea typically
remains clear. In keratoconus posticus circumscriptus, there may be
one, or occasionally more, central or paracentral areas of posterior
% excavation associated with variable amounts of stromal scarring (Fig.
73.18). Corneal guttae are often seen within the area of involvement,
Fig. 73.16 Keratoglobus appearance. (A) The typical globular contour of and pigment is sometimes found at the peripheral edge of this poste-
the keratoglobus can be seen in this cornea photographed in profile. (B) rior lesion.
Generalized thinning is common (1), with the greatest thinning found in While corneal astigmatism can occur, it is generally not the high
the periphery.
irregular astigmatism seen in keratoconus.193 This relative lack of
involvement of the anterior refractive surface explains why posterior
keratoconus results in only mild to moderate reduction in visual func-
Unlike keratoconus, keratoglobus is not associated with atopy, tion. Vision decrease, when it occurs, is usually caused by stromal scar-
tapetoretinal degeneration, or hard contact lens wear. Acquired kera- ring, associated ocular disease, or amblyopia. Corneal topography has
toglobus has, however, been described in association with vernal kera- demonstrated central steepening in the area of posterior excavation as
toconjunctivitis186 and hyperthyroidism.187 well as surrounding flattening.
While there is no association with Down syndrome, keratoglobus Posterior keratoconus is developmental, usually nonprogres-
has been reported in association with Rubinstein-Taybi syndrome, in sive, noninflammatory, and usually unilateral.29 Bilateral involve-
which intellectual impairment occurs.188 As in keratoconus, there is ment, however, is not uncommon.194 Acquired cases occur and are
evidence to suggest an association with abnormalities of connective usually associated with trauma.195 The histopathologic findings in
tissue. Keratoglobus and blue sclera have been linked to other findings, posterior keratoconus have been described.196,197 Irregular epithe-
such as hyperextensible joints, abnormalities in teeth and hearing, a lium with focal disruption of the epithelial basement membrane is
high incidence of fractures, and consanguinity.187 seen, and BL is replaced with fibroblastic proliferation. The stroma
Keratoglobus associated with other disorders of connective tis- is thin with lamellar disorganization. The central portion of the
sue bears some resemblance to the ocular form of Ehlers-Dan- Descemet membrane is not thin but may show marked disorga-
los syndrome, but keratoglobus patients do not demonstrate skin nization. A ring of thickened Descemet membrane at the edge of
CHAPTER 73 Noninflammatory Ectatic Disorders 765
1 2
Fig. 73.17 Keratoglobus topography. (1) Orbscan II (Bausch and Lomb) power map reveals diffuse steepen-
ing with the flattest Sim K reading 51.9 diopters; (2) pachymetric map shows diffuse thinning, with the inferior
part of the cornea being thinnest.
2 2
1
$ %
Fig. 73.18 Posterior keratoconus. (A) In the localized form an area of relative lucency (1), which corresponds
to the site of posterior excavation, is surrounded by stromal scarring (2). (B) This slit view demonstrates
thinning (1), which results from steepening in the posterior corneal contour. The anterior corneal contour is
relatively unaffected.
766 PART VII Diseases of the Cornea
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mol 2005;33(1):47–52.
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Clinically, there are similarities between posterior keratoconus (Copenh) 1992;70(1):111–4.
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