It happens to all of us. The situation is a consultation with a newly diagnosed keratoconus patient. You are describing the condition, the changes that it causes in corneal structure, and its tendency to develop. The patient asks, “But, where does it come from?” You explain that we don’t have all of the data, but because more than 50 gene loci are related to keratoconus (Wang and Pang, 2019), we can only presume that a large chance exists that any particular patient’s keratoconus was passed on by his or her parents. Patients, or their accompanying parents, may chime in at this point that keratoconus has never been diagnosed in the parents or in any other close relatives.

This is when I reach into my office library for my copy of a classic reference on this subject. Rabinowitz (1998), in his article that published well before all of the 20,000 to 25,000 genes in the human genome were elucidated, showed several family trees of keratoconus patients going back as many as four or five generations. He populated his trees with the ocular signs familiar to us all that can signify keratoconus; corneal thinning, increased and increasingly irregular corneal astigmatism, corneal steepening, Fleischer’s ring, Vogt’s striae in Descemet’s membrane, and scissors reflex on retinoscopy make up the greater part of the list. In most cases, the family members did not have keratoconus but rather only one or more disparate signs. He concluded that when discussing phenotypes in the absence of absolute genotyping, family members who exhibit signs can indicate a greater likelihood of a relation developing the disease.

A Case of Not Exactly Keratoconus

A 37-year-old woman who had never been diagnosed with keratoconus has two brothers who are positive for the condition. She presented to her ophthalmologist with a complaint of poorer vision in her left eye; her optometrist had been unable to improve her vision with glasses.

The consideration was that, even at her age, keratoconus had begun to develop. This was a head-turner, as most cases of keratoconus are diagnosed or at least suspected before the age of 20. Her age can nearly rule out the diagnosis of a new case. The possibility existed that she was seeing primarily with one eye while the other eye developed the disease, as asymmetry can often manifest in keratoconus. The physician referred her to me for my considered opinion.

As it turned out, the refraction was reasonable: a minor, balanced amount of myopia and a similarly minor and balanced amount of astigmatism in each eye to excellent visual acuity, with uncomplicated retinoscopic reflexes. Her corneae were clear of keratoconus signs. At this stage, had I simply returned the patient to the referring ophthalmologist, we would have been none the wiser, and the patient would be clear of any suspicion that she had eyes like her siblings.

To complete the picture, however, we acquired tomography of each eye (Figure 1). Here, the story becomes more intriguing. While clear and obvious keratoconus was not observed, she has suggestive signs: her corneae were around 480µm at their thinnest (534μm is considered normal, with a 95% confidence interval of 0.473μm to 0.595μm) (Smadja et al, 2013); posterior corneal elevation was around +5 in each eye (+13 begins to be suspect) (Henriquez et al, 2020); her anterior corneal topography was not perfectly clear and defined, but she had been wearing soft contact lenses when she arrived. In summary, before accepting a diagnosis of active keratoconus, forme fruste keratoconus and subclinical keratoconus are alternatives that must be considered.

To say that this patient has keratoconus would not be correct; but on the other hand, to say that she has normal corneae would not reflect the value of our findings. A follow-up visit in three months with a review of the refraction and tomography would probably show stability in all of the measures that we obtained. In conclusion, our diagnosis then would probably be stable, regular corneae with corneal thinning.

So, while our patient had no overt keratoconus herself, she has a family history and subtle signs. In another decade or so, when her child who is developing visual problems asks for help and claims that neither of his or her parents had keratoconus, the mother might remember this encounter. Her child might know of his or her uncles’ eye problems, or perhaps not. In any event, this case demonstrated a genetic fact that should be enshrined in this family’s medical history. CLS

Acknowledgement: As always, I express my respect and thanks to my patients for choosing me to help them confront their visual adversities invoked by their corneal ectasias.

For references, please visit www.clspectrum.com/references and click on document #312.