At the completion of this article, the reader should be able to improve their management of keratoconus, including:
- Understand clinical signs and symptoms of keratoconus
- Review surgical and non-surgical treatment and management options
- Identify the demographic groups at risk for keratoconus
- Understand the critical importance of early identification, especially with imaging, of keratoconus patients and suspects
- Feel confident investigating or referring suspicious cases.
A/Prof Abi Tenen
MBBS(Hons) FRANZCO
Vision Eye Institute
The pathogenesis of keratoconus is not well understood but it is a condition that can be practically managed to prevent visual deterioration and stabilise the condition. Delayed diagnosis results in lost vision, which is why early identification through patient history, eye exams and especially corneal imaging is so critical, writes ABI TENEN.
Understanding, diagnosing and managing keratoconus seems to be confusing for many, but why? Probably because nobody really knows for sure what causes it, how common it is and the best way to treat it.
Perhaps the condition seems tricky because it’s not a single disease entity but rather a consequence of various pathologies. This idea could mean that the corneal ectasia we see in keratoconus is a consequence of various disease processes in the same way that inflammatory arthritis is the consequence of various autoimmune diseases. Like arthritis, keratoconus could be the ‘effect’ rather than the ‘cause’. It’s interesting to ponder this possibility and the topic is open to debate.
Certainly, keratoconus presents along a spectrum. It can present as very mild thinning or corneal asymmetry with normal vision. It can also present as severe corneal collapse with scarring and corneal blindness, or it could be anywhere in between these two extremes.
The patients with mild corneal thinning or steepening may not fit the classic diagnostic criteria of keratoconus but they are arguably on the spectrum. These are the patients who may be deemed suitable for surface laser treatments such as PRK but not deeper corneal procedures such as LASIK. It’s not uncommon to find keratoconus among family members of a PRK patient who presents with these milder findings.
Keratoconus also has ‘clinical cousins’: pellucid marginal degeneration and post-LASIK ectasia are variations which essentially fall under the same disease category but follow distinctly different patterns.
Complex genetics
New information is constantly being offered up as research projects delve deep and diagnostic technology advances, which is all very exciting. But we are only at the tip of the iceberg in terms of unravelling the vastly complex underlying genetic associations with one gene location on chromosome 11 showing consistent relevance,1 however, genome-wide analysis has found significant association between 36 gene locations and keratoconus.
Needless to say, the genetics are complex.
Results of genetic studies also suggest ‘pleiotropy’, which means that some disease mechanisms are genetically shared with other corneal conditions such as Fuch’s dystrophy. 2 This is interesting because, clinically, these two diseases are unrelated, except that they both involve the cornea.
There’s a lot we don’t know yet, but we do have enough information to deal with keratoconus practically in a clinical setting. To boil it down: what matters is detecting keratoconus, stabilising it and correcting the vision. The earlier this is achieved, the better. That’s the take home message.
Despite the gaps in our knowledge, there’s a lot we do know about the condition, so let’s look at the topic in more detail.
Clinical signs and symptoms
Keratoconus presents as a progressive thinning and bulging (ectasia) of the cornea which is bilateral but usually asymmetrical. It tends to present with increasing visual impairment mostly due to unstable refractive error (astigmatism is key) and debilitating symptoms such as glare, ghosting or diplopia. In more advanced cases hydrops, scarring and even perforation may result.
Who is at risk?
Most patients present at a younger age (10-30 years) although progressive disease has been reported in older decades all the way up to 77 years.3
It isn’t an uncommon condition; there is a global prevalence of about one in 500, however, the numbers are uncertain and are very likely higher with one recent report suggesting prevalence of one in 84.4
There are hot spots for keratoconus in some communities – it’s more common in the Middle East, parts of India and among the Māori population in New Zealand; Australia has quite a high incidence of keratoconus, mostly among people who originate in above listed regions. Consanguinity is a contributing risk factor in the genetic analysis of highly affected populations.
Keratoconus is also associated with conditions such as Down Syndrome and Marfan Syndrome, which highlights the genetic component to the disease.
Things that exacerbate the condition
Mechanical, pro-inflammatory stimuli such as eye rubbing or poorly-fitted contact lenses can progress keratoconus. This, alongside more recent findings, supports the theory that keratoconus is an immune-mediated inflammatory degenerative process, although in the past it has been widely categorised as a non-inflammatory process.5
Treatment and management options
Collagen cross-linking (CXL) is commonly used to prevent progression of keratoconus and, in younger patients, plays a prophylactic role in terms of preventing early vision loss. Various protocols exist and for the classic epithelium-off technique, minimal corneal pachymetry of 400 microns is recommended.
Vision correction can be offered using non-surgical methods including spectacles (sometimes with specialised technology such as wavefront treated lenses), soft contact lenses, rigid gas permeable lenses or specialised lenses (piggy-back, hybrid, miniscleral and scleral). Making sure that the ocular surface is well lubricated and paying attention to allergies with, for instance, antihistamine or mast cell stabilising eye drops can also assist visual quality and patient comfort.
Surgical management, aside from CXL, may include: intracorneal ring segments such as Keraring; CAIRS (corneal allogenic intrastromal ring segments); topography guided surface excimer laser ablations; and corneal grafting techniques, usually deep anterior lamellar keratoplasty (DALK) or penetrating keratoplasty (PK).
PK or full thickness corneal transplant is now uncommonly performed for keratoconus and would be indicated in situations such as post hydrops. Thankfully, corneal grafting as a whole is rarely required since the advent of CXL, which really can be thought of as not just a stabilising procedure but a graft preventing procedure. Of course, not every cross-linked patient will escape progression and the need for an eventual graft, especially if they continue to enthusiastically rub their eyes.
The importance of early identification of patients and suspects
Detection of keratoconus will partly depend on access to diagnostic equipment, but everybody can check the following:
- history of changing vision
- history of eye rubbing and allergy
- changing refraction and particularly astigmatism
- family history of keratoconus
A young patient with rapidly-changing refraction, particularly with astigmatism, in addition to any of the known risk factors is highly suspicious. These patients need corneal imaging straight away or at the very least, look for distorted mires.
Topographic diagnoses
Imaging is the most reliable way to objectively find keratoconus and it doesn’t really matter which type of topographer or tomographer is used, they will all pick up corneal steepening and thinning.
Scheimflug imaging and elegant anterior OCT devices with features such as epithelial mapping provide valuable information, but for the purposes of detecting keratoconus and referring to ophthalmology, suspicious corneal shape and thinning pachymetry are more than enough to raise alarm.
Fortunately, the reduced cost and increasing availability of topographers means that more optometry practices than ever now have the ability to make a topographic diagnosis. Don’t wait until you’re confident that you’re seeing a scissor reflex, Fleischer rings, Voigt’s striae, oil droplet sign or Munson’s sign – by then the disease may be significantly progressed and the patient could lose the opportunity to be stabilised with CXL.
Also, don’t wait until you’ve documented several refractive shifts with deteriorating best corrected visual acuity. Again, the patient misses out on the opportunity to be stabilised early with the chance of holding on to better vision.
When is the best time to image?
Suspicion of keratoconus is enough to justify imaging, it’s a non-invasive test that can be done quickly with definitive results. The earlier this is done the better – and then the patient can be assessed for CXL.
Any young patients with keratoconus or older patients with evidence of progressive keratoconus should be referred to an ophthalmologist who performs cross-linking. Likewise, any patients with suspicion of keratoconus and/or who requires corneal imaging that may not be available to the referring optometrist, should be referred too.
Identifying the risk factor of eye rubbing and advice against it, along with management of any ocular allergy symptoms, should also be tended to without delay. Of course, spectacle and contact lens prescription closes the loop of the detection/stabilisation/vision correction triad.
Informed referral and patient co-management
Bear in mind that if your patient is likely to require CXL soon, then their refraction will most likely fluctuate and change after the treatment while the cornea is remodelling and stabilising. This means that any vision correction prescribed during the stabilisation period is unlikely to be useful for very long and will need to be updated regularly. If you are planning contact lenses for a patient referred to CXL, it may be worth waiting until a few months post-op before considering the high-tech lens options but, of course, this would need to be assessed on an individual basis.
Likewise, if the patient is to be considered for any of the other keratoconic corneal surgeries, it makes sense to understand the timeframe and pathway to surgical treatment before a prescription is actioned to the relevant eye. Ask the doctor directly when the patient should see you for a new prescription and tell them what you are planning to do.
Open communication in both directions is important so that patients receive the optimal treatment at the optimal time. Patients appreciate smooth co-management, and nobody likes wasted time and resources which tends to result when practitioners aren’t ‘on the same page’.
Imaging the cornea
Ophthalmologists managing keratoconus are generally very happy to assess if there’s doubt about the diagnosis. Sometimes what looks like keratoconus clinically is just high regular corneal astigmatism and sometimes what doesn’t look like keratoconus clinically is actually early cone. Imaging the cornea takes the guesswork out of the equation.
Here are a couple of examples where corneal maps evidently demonstrate the diagnosis of keratoconus, making management decisions straightforward, whereas history and clinical findings did not clearly raise suspicion.
Case 1
This 30-year-old patient (Figure 1) only had 1.75 D of cylinder in their glasses and good BCVA, so the maps seem surprising. They had been wearing spectacles for 15 years and were rubbing their eyes with gradual visual decline over recent years but no significant symptoms or slit lamp signs. (The left and right corneas looked similar on imaging).
Case 2
This 39-year-old patient (Figure 2) presented with normal vision in the left eye and poor vision in the right. Corneal maps show keratoconus with significant asymmetry. The patient hadn’t really noticed visual difficulty as the left eye was compensating for the right. Sometimes these cases are misdiagnosed as unilateral amblyopia if the cornea is not properly examined and/or imaged. The right cornea at presentation was too advanced for CXL and was booked for deep anterior lamellar keratoplasty (DALK). The left cornea looked almost normal and observation with serial imaging was planned. It will possibly require CXL in future if deterioration is detected. The patient does not rub their eyes.
Conclusion
In many ways, with the prevalence of keratoconus showing itself to be much higher than once thought, the clinical decision to only observe (i.e., watch the patient deteriorate without offering active treatment) is no longer enough. Patients will only be upset if they find out later that they’ve had keratoconus all along and they weren’t given the opportunity to stabilise it.
Remember that children with keratoconus can progress very rapidly, leading to devastating visual decline, so refer these patients urgently. Sometimes this may seem like an inconvenience to parents and carers, particularly if the patient needs to travel from rural areas to the nearest city. Spending time to explain the relevance of urgent medical review is an important first step in what will be a lifelong journey for the patient.
It’s worth noting that patients often self-educate online and although their information sources may be unverified or inaccurate, this means that they are generally aware of current medical treatments and sometimes present for professional help already self-diagnosed. This can be either helpful or problematic. Don’t be deterred and stick to your plan.
Finally, patients and/or parents and carers of patients always appreciate a practitioner who takes the time to thoroughly discuss with empathy what can be a frightening diagnosis. A good ‘bedside manner’ not only gives patients reassurance and confidence, but it can also actually result in better clinical outcomes as practitioner attitude and demeanour can have a positive placebo effect, particularly in terms of reducing patient anxiety.
More reading
Living with keratoconus: Highlights from KeraClub 2023
CPD: The role of the optometrist in keratoconus
CAIRS Plan tool to streamline keratoconus surgical procedures
References
1.McComish BJ, Sahebjada S, Bykhovskaya Y, […], Tenen A, et al. Association of genetic variation with keratoconus. JAMA Ophthalmol. 2020; 138(2): 174–181. (Published online) doi:10.1001/jamaophthalmol.2019.5293.
2. Hardcastle AJ, Liskova J, […] Tenen A, et al. A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus. Commun Biol. 2021; 4 (1): 1–13. (Published online) doi:10.1038/s42003-021-01784-0.
3. Burton O, Tenen A and Hodge C. First presentation of keratoconus in a geriatric patient: diagnosis and treatment of late progression. JCRS Online Case Reports. 2019; 7(4): 65–70. (Published online) doi:10.1016/j.jcro.2019.09.004.
4. Chan E, Et Al. Prevalence of Keratoconus Based on Scheimpflug Imaging: The Raine Study. Ophthalmology. 2021 Apr; 128 (4): 515-521.
5. Shetty R, Khamar P, Kundu G, Ghosh A, Sethu S. Inflammation in Keratoconus. In Keratoconus 2023 Jan 1 (pp. 159-168). Elsevier.
