April 2019

CORNEA

Presentation Spotlight
Macular choroidal thickening in keratoconus patients


by Stefanie Petrou Binder, MD EyeWorld Contributing Writer


An image obtained with the Deep Range Imaging OCT-1 Atlantis
Source: Topcon

 

A new study found that the choroid in eyes of patients with keratoconus is significantly thicker than those of healthy controls. Increased choroidal thickness is less evident in individuals 45 years or older, when keratoconus is thought to have reached stability, according to Jorge Ruiz-Medrano, MD, who reported the outcomes of his study at the 36th Congress of the European Society of Cataract and Refractive Surgeons (ESCRS).

Swept source OCT of the fovea

The prospective, cross-sectional study included 102 eyes from 51 keratoconus patients and used swept source OCT to determine whether patients suffering from different stages of keratoconus present with alterations of their choroidal thickness profile. The study included eyes with both a clinical and topographic diagnosis of keratoconus, only including high quality images. Eyes with ocular trauma, retinal diseases, any eye tumor pathology, and an axial length in excess of 26 mm were excluded.
Examinations were conducted in both eyes to avoid bias and comprised Pentacam (Oculus) images to determine the Amsler-Krumeich classification for keratoconus, IOLMaster 500 (Carl Zeiss Meditec) measurements for axial length, Triton swept source OCT (Topcon) to measure choroidal thickness, as well as comparisons to age- and gender-matched healthy controls. The choroidal thickness was measured manually in the subfovea and involved three nasal measurements and five temporal measurements.
“Keratoconus patients clearly show thicker choroids than healthy controls at all patient ages and levels of keratoconus. The clear, statistically significant difference in choroidal thickness seems to be slightly less when patients are 45 years or older, which is the point, in theory, that keratoconus becomes more stable,” Dr. Ruiz-Medrano said.
When compared, disease severity versus choroidal thickness revealed noteworthy outcomes. “If you look at the degree of keratoconus, we see that the more severe the keratoconus, the thicker the choroid. While those differences did not reach statistical significance, we clearly saw a trend in that direction, which might have shown statistical significance in a larger patient collective,” he said.
Dr. Ruiz-Medrano noted that in individuals with one-sided keratoconus, the choroid thickness measurements in the affected eye were frequently significantly increased compared to the unaffected side, with the normal, subfoveal choroid measuring between 250 and 280 µm in one eye and the central foveal choroid in the keratoconic eye measuring approximately 1000 µm.
Discrepancies in the choroid thickness between partner eyes was a subject investigated by Dr. Ruiz-Medrano in a previous study.1 The study included 140 eyes of 70 healthy patients that were measured with swept source OCT to determine any potential differences in the macular choroidal thickness profile. He noted thicker macular nasal choroid measurements in the right compared to the left partner eyes. Subfoveal and temporal choroid thickness, however, were not found to be different between eyes.

Theories behind keratoconus

Keratoconus patients show degradation of the basal membrane, Bowman’s layer, stroma, as well as Descemet’s membrane in later stages of disease progression. The key component in the alterations found in the choroid layer is related to defective collagen. The choroid is composed of the same types of collagen as the corneal stroma.
“In keratoconus, the collagen distribution is diminished and disorganized.2 The collagen in the cornea is mostly type I, about 75%, but we also find types III, V, VI, IX, XII,” Dr. Ruiz-Medrano said. “The choroid is mostly made of vessels and adventitia. We see that collagen type I is the main component of the media and adventitia of the choroidal vessel walls and may be partially responsible for the changes in keratoconus. However, this does not fully explain the problem because if the collagen defect is genetic, it should worsen compared to the healthy population. We need to look for another explanation that looks beyond a genetic origin.”
According to the observations of an unrelated trial that investigated the subfoveal choroidal thickness in the eyes of individuals suffering from different inflammatory diseases including Vogt-Koyanagi-Harada disease, Behcet’s disease, psoriasis, and ankylosing spondylitis, all of these entities were associated with thickened choroids. The investigators related the choroidal thickening to inflammatory infiltration and increased exudation.3 Yet another study found that keratoconus, while associated with genetic and environmental factors, has an inflammatory component involving proteolytic enzymes, cytokines, and free radicals. The investigators performed a literature review of published biochemical changes in keratoconus that supported this observation.4 Finally, the corneal epithelium demonstrated elevated MMP-9 levels and inflammatory cytokine expression in tears of keratoconus patients, with MMP-9 levels reduced and the disease progression arrested after the use of cyclosporine, according to another study done on the subject. The investigators suggested cyclosporine as a possible novel treatment strategy in keratoconus.5
“Keratoconus is the most frequent ecstatic disorder, affecting 2,300,000 people in the U.S. alone,” Dr. Ruiz-Medrano said. “It is associated with progressive myopia and astigmatism and is usually detected at puberty, worsening progressively until the third or fourth decade of life, when it generally stabilizes. Our observations in this study support theories about an inflammatory origin of keratoconus. Our theory is that the choroidal thickening observed in keratoconic eyes may be inflammatory in nature.”

About the doctor
Jorge Ruiz-Medrano, MD
Jules Gonin Eye Hospital
Lausanne, Switzerland

References

1. Ruiz-Medrano J, et al. Asymmetry in macular choroidal thickness profile between both eyes in a healthy population measured by swept-source optical coherence tomography. Retina. 2015;35:2067–73.
2. Chaerdaky R, et al. The keratoconus corneal proteome: loss of epithelial integrity and stromal degeneration. J Proteomics. 2013;87:122–31.
3. Maruko I, et al. Subfoveal choroidal thickness after treatment of Vogt-Koyanagi-Harada disease. Retina. 2011;31:510–7.
4. Galvis V, et al. Keratoconus: an inflammatory disorder? Eye (Lond). 2015;29:843–59.
5. Shetty R, et al. Elevated expression of matrix metalloproteinase-9 and inflammatory cytokines in keratoconus patients is inhibited by cyclosporine A. Invest Ophthalmol Vis Sci. 2015;56:738–50.

Financial interests
Ruiz-Medrano
: None

Contact information
Ruiz-Medrano
: jorge.ruizmedrano@gmail.com

Macular choroidal thickening in keratoconus patients Macular choroidal thickening in keratoconus patients
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