Schnyder corneal dystrophy (SCD) previously called Schnyder
crystalline corneal dystrophy (SCCD) is a rare autosomal, dominantly inherited
bilateral disease affecting both sexes with equal probability. The causative
gene is localized on chromosome 1p36 (1) and called UBIAD1 (UbiA
prenyltransferase domain-containing protein1) (2,3). This gene is involved in
cholesterol metabolism. This disorder is characterized by abnormal deposition
of cholesterol, phospholipids and recently suggested sphingomyelin mainly in
the cornea(4-6), however systemic association such as genu valgum (4%) and
hypercholesterolemia (66%) is also observed (7).
Tipically the bilateral ring-shaped or disciform central opacities are found in
clinical exam, which usually consist of fine, polychromatic, needle-shaped or
rectangular crystals, but sometimes disciform opacity can be present without
any evidence. In fact, 46% of SCD eyes have no subepithelial crystals (3),
which may delay a diagnosis until the fourth decade, when normally recognised
in the first, second decade of life (5). Consequently, Weiss (8) and then the
International Committee for the Classification of Corneal Dystrophies (9)
removed “crystalline” from the nomenclature.
The diagnosis of SCD is usually based on clinical findings. Histochemical and
electron microscopy studies are utilized in a diagnosis confirmation, but the
corneal tissue is available only after surgical intervention.
In vivo corneal confocal microscopy allows to perform noninvasive real-time
spatial sectioning of living corneal tissues at the cellular level (10,11). The
clinical usefulness of this method has been documented in studies of both
normal human corneas (12) and corneas affected by dystrophy (13,14), including
SCD (15). In vivo laser scanning confocal microscopy (LSCM) (HRT3/Rostock
Cornea Module; Heidelberg Engineering GmbH, Dossenheim, Germany) permits more
detailed in vivo layer-by-layer observations of corneal microstructure with an
axial resolution of nearly 4 micrometers, much better than that obtained with
conventional white-light confocal microscopes [for instance, 10 micrometers
axial optical resolution with ConfoScan 2 (Nidek Technologies, Vigonza, Italy)]
and incomparably better than that with biomicroscopy. The possibility of in
vivo evaluation of corneal morfology gives us also spectral optical coherence
The purpose of this case report is to present the results of noninvasive
real-time studies: confocal microscopy and spectral optical coherence
tomography and their utilization in handling SCD case.
A 68-year-old man was referred to our clinic with the diagnosis of Schnyder
corneal dystrophy and with the symptoms of photophobia, glare and low visual
acuity (VA) more affected in photopic condicions. VA in a lit room was 0.04 in
the right eye and 0.02 in the left eye which did not improve with correction
and corneal sensation was reduced. Slit-lamp biomicroscopy revealed bright,
refractile crystals in the anterior stroma of the central and paracentral
cornea bilaterally. Patient had severe panstromal disk-like opacity affecting
pupillary axis, prominent arcus (senilis) lipoides in both eyes and
mid-peripherial corneal haze that fills in the area between the corneal opacity
and the peripherial arcus (Fig. 1). Fundus examination was not possible
because of medias opacity. US B exam showed retina attached in both eyes. A
LSCM with a diode laser of 670 nm wavelenght (HRT3/RostockCorneaModule:
Heidelberg Engineering, Drossenheim, Germany) was also performed obtaining
two-dimensional confocal images of the different corneal layers. Normal
epithelial cells, large accumulations of hiperreflective rectangular and
needle-shaped material in the subepithelial and anterior stroma were observed.
The basal epithelial/ subepithelial nerve plexus and fibres were absent and the
keratocytes of mid and posterior stroma were not visualized properly probably
because of hiperreflection of anterior structures. Due to the same reason the
endothelial cells were not seen (Fig. 2). Subsequently, the corneas of the
patient were scanned with central anterior asterisk scan patterns, by a
high-speed, high-resolution, spectral optical coherence tomography (SOCT
Copernicus Plus: Optopol, Zawiercie, Poland). The images obtained indicated
that the crystalline deposits were localized within the anterior stroma and
reflectivity of Descemet membrane and endothelial cells was increased (Fig. 3).
The serum lipid levels showed hypercholesterolemia (HDL 66 mg/dl) and
hypertriglyceridemia (TG 184 mg dl) although the patient was on medical
treatment from the moment of the myocardial infarction. He did not refer the
genu valgum nor family history of corneal disease.
The patient underwent penetrating keratoplasty (PKP) in the left eye. Immediate
postoperative evaluation reveled: VA 0.06 in the left eye and the slit-lamp
examination showed corneal button to be transparent with a few Descement folds.
No evidence of epithelial defect was observed (Fig. 4). After 2 months
follow-up the VA is 0.1 and BCVA is 0.3 in the left eye and the corneal graft
remained transparent (Fig. 5).
Weiss (7) reported that patients with SCD older than 39 years had evidence of
diffuse stromal haze occuppying the whole diameter of the cornea, which causes
significant decrease of VA as seen in case of our 68-year-old patient.
Cholesterol crystals may affect VA by diffraction of light, resulting in glare
and photophobia, major complaints of our patient.
Morphological evaluation on SCD by in vivo LSCM and SOCT serve to clarify the
clinical findings of this disease. The glare and the photopic visual acuity
diminished is caused by light dispersion on the deposits of crystalline
material in the anterior stroma. LSCM and SOCT highlighted in our case the
morphological changes at the level of Bowman’s membrane and anterior stroma
with an accumulation of crystalline deposits, which is consistent with the
result of the previous histological study of SCD (16-18). The reduced corneal
sensation postulated by Wiess (7) found an explication by revealing that the
basal epithelial/subepithelial innervation is destroyed in older patients. As
our patient belongs to the group with the most advanced corneal changes and the
most prominent symptoms according to Weiss classification based on corneal
findings with patient’s age (5), we observed the alteration of nerve structures
and we found the corneal sensation decreased.
Other finding from in vivo LSCM study is that the shape and numbers of
crystalline deposits in the anterior stroma differ among patients despite quite
similar clinical appearance (18). Whether an association between deposit size
and numbers and genotype exist, needs further confocal and mutiational analysis
using a large number of patients with SCD as suggested in Kobayashi study (19).
Unfortunately, there is no local or systemic medical treatment available to
stop the progression of corneal lipid deposition resulting in cornea
opacification. Recognized surgical methods are phototherapeutic keratectomy (PTK),
penetrating keratoplasty (PKP) and deep anterior lamellar keratectomy (DALK).
The choice of the treatment depends on the case severity and the depth of
lipids deposits. In the early stages when we have only subepithelial
distribution of crystalline material we can use the PTK to obtain visual acuity
improvement. It is considered to prevent accumulation of crystaline deposits in
the anterior stroma better then anterior keratectomy (14) and compared with PKP
and DALK is a less invasive method, but is effective only when the crystals are
located in superficial cornea (20). The choice between PKP and DALK is also
based on the depth of corneal affectation. Weiss (5) showed that, contrary to
what is usually assumed, SCD affected the entire thickness of the corneal
stroma in the majority of elderly patients, although the crystals were always
subepithelial. Dissolved cholesterol or lipid or both have even been found in
the basal epithelial cells and endothelial cells (3). Affectation of
endothelium makes the selection of DALK impossible. This is the reason why
study of corneal morphology in vivo is so important. The analysis of corneal
structures helps to make the right decision on the surgery method and confocal
microscopy and OCT contribute far more information than biomicroscopy, even if
the resolution of the images of the more posterior structures is decreased
because of the high reflectivity of the more anterior structures caused by
intense crystalline deposition (14). We opted for PKP as the best choice for
our patiens because of SOCT (hiperreflectivity of posterior complex: Decemet
membrane and endothelium) and LSCM (increase reflectivity of stroma) images
strongly suggested the entire cornea affectation. The choice of PKP among
elderly patients is concerned with the results of Weiss study which
demonstreted that the incidence of PKP depends on patients age and that among
elderly patients amounts to 77% (7).
In conclusion, in vivo laser confocal microscopy and spectral optical coherent
tomography, new emerging non-invasive technologies, proved to be a useful tool
in SCD handling.
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Fig. 1. Slit-lamp biomicroscopy – the right and left cornea
with severe panstromal central disk-like opacity, prominent arcus lipoides and
mid-peripherial corneal haze. The anterior stroma of the central and
paracentral with crystallline deposits.
Ryc. 1. Lampa szczelinowa – rogówki prawa i lewa z dyskoidalnym centralnym
zmętnieniem śródmiąższowym, wyraźnie zaznaczoną obwódką starczą i przymgleniem
wypełniającym przestrzeń między zmętnieniem centralnym a obwódką starczą. Osady
krystaliczne znajdują się w przedniej części istoty właściwej centralnej i
Fig. 2. In vivo laser scanning confocal microscopy – a.
normal basal epithelial cell layer,
b. subepithelial stroma, c. anterior stroma, d. midstroma with numerous
rectangular and needle- shaped crystals and increased background intensivity,
e. keratocyte nuclei undetectable in mid and posterior stroma.
Ryc. 2. In vivo laserowa skaningowa mikroskopia konfokalna – a. prawidłowa
warstwa nabłonkowa, b. podnabłonkowa część istoty właściwej, c. przednia istota
właściwa, d. środkowa istota właściwa z dużą liczbą kryształów czworokątnych i
w kształcie igły oraz zwiększoną intensywnością tła, e. keratocyty z
niewidocznymi jądrami w częściach istoty właściwej – środkowej i tylnej.
Fig. 3. Spectral optical coherence tomography –
hiperreflecivity of crystalline deposits localized within the anterior stroma
and hyporeflecivity of more profund layers of the both corneas,
hiperreflectivity of Descemet membrane.
Ryc. 3. Spektralna koherentna tomografia optyczna – hiperrefleksyjne pasmo
złogów w przedniej istocie właściwej oraz hiporefleksyjność głębszych warstw
obu rogówek, hiperrefleksyjność błony Descemeta.
Fig. 4. Slit- lamp biomicroscopy – the left eye in the 12th
day after PKP.
Ryc. 4. Lampa szczelinowa – lewe oko w 12. dobie po keratoplastyce drążącej.
Fig. 5. Slit- lamp biomicroscopy – the left eye in the 2nd
month after PKP.
Ryc. 5. Lampa szczelinowa – lewe oko 2 miesiące po keratoplastyce drążącej.